16936704|t|An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. 16936704|t|Observational studies have suggested that psychometric psychosis liability and a functional polymorphism in the catechol-O-methyltransferase (COMT Val(158)Met) gene moderate the psychosis-inducing effect of cannabis. To replicate and extend this finding, a double-blind, placebo-controlled cross-over design was used in which patients with a psychotic disorder (n=30), relatives of patients with a psychotic disorder (n=12), and healthy controls (n=32) were exposed to Delta-9-tetrahydrocannabinol (Delta-9-THC, the principal component of cannabis) or placebo, followed by cognitive assessment and assessment of current psychotic experiences. Previous expression of psychometric psychosis liability was also assessed. Models of current psychotic experiences and cognition were examined with multilevel random regression analyses to assess (i) main effects of genotype and condition, (ii) interactions between condition and genotype, and (iii) three-way interactions between condition, genotype, and psychometric psychosis liability. Carriers of the Val allele were most sensitive to Delta-9-THC-induced psychotic experiences, but this was conditional on prior evidence of psychometric psychosis liability. Delta-9-THC impacted negatively on cognitive measures. Carriers of the Val allele were also more sensitive to Delta-9-THC-induced memory and attention impairments compared to carriers of the Met allele. Experimental effects of Delta-9-THC on cognition and psychosis are moderated by COMT Val(158)Met genotype, but the effects may in part be conditional on the additional presence of pre-existing psychosis liability. The association between cannabis and psychosis may represent higher order gene-environment and gene-gene interactions. 16936704 25 53 catechol-o-methyltransferase Gene 1312 16936704 78 106 delta-9-tetrahydrocannabinol Environment 1312-D011618 16936704 126 135 psychosis Disease D011605 16936704 55 64 psychosis Disease D011605 16936704 112 140 catechol-O-methyltransferase Gene 1312 16936704 142 146 COMT Gene 1312 16936704 178 187 psychosis Disease D011605 16936704 207 215 cannabis Environment 1312-D011618 16936704 264 269 blind Disease D001766 16936704 342 360 psychotic disorder Disease D011618 16936704 398 416 psychotic disorder Disease D011618 16936704 620 629 psychotic Disease D011618 16936704 679 688 psychosis Disease D011605 16936704 736 745 psychotic Disease D011618 16936704 1012 1021 psychosis Disease D011605 16936704 1083 1094 Delta-9-THC Environment 1312-D011618 16936704 1103 1112 psychotic Disease D011618 16936704 1185 1194 psychosis Disease D011605 16936704 1316 1327 Delta-9-THC Environment 1312-1 16936704 1336 1368 memory and attention impairments Disease 1 16936704 1433 1444 Delta-9-THC Environment 1312-D011618 16936704 1433 1444 Delta-9-THC Environment 1312-1 16936704 1462 1471 psychosis Disease D011605 16936704 1489 1493 COMT Gene 1312 16936704 1602 1611 psychosis Disease D011605 16936704 1647 1655 cannabis Environment 1312-D011618 16936704 1647 1655 cannabis Environment 1312-1 16936704 1660 1669 psychosis Disease D011605 15217512|t|Oestrogen receptor alpha gene haplotype and postmenopausal breast cancer risk: a case control study. 15217512|t|INTRODUCTION: Oestrogen receptor alpha, which mediates the effect of oestrogen in target tissues, is genetically polymorphic. Because breast cancer development is dependent on oestrogenic influence, we have investigated whether polymorphisms in the oestrogen receptor alpha gene (ESR1) are associated with breast cancer risk. METHODS: We genotyped breast cancer cases and age-matched population controls for one microsatellite marker and four single-nucleotide polymorphisms (SNPs) in ESR1. The numbers of genotyped cases and controls for each marker were as follows: TAn, 1514 cases and 1514 controls; c.454-397C --> T, 1557 cases and 1512 controls; c.454-351A --> G, 1556 cases and 1512 controls; c.729C --> T, 1562 cases and 1513 controls; c.975C --> G, 1562 cases and 1513 controls. Using logistic regression models, we calculated odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype effects were estimated in an exploratory analysis, using expectation-maximisation algorithms for case-control study data. RESULTS: There were no compelling associations between single polymorphic loci and breast cancer risk. In haplotype analyses, a common haplotype of the c.454-351A --> G or c.454-397C --> T and c.975C --> G SNPs appeared to be associated with an increased risk for ductal breast cancer: one copy of the c.454-351A --> G and c.975C --> G haplotype entailed an OR of 1.19 (95% CI 1.06-1.33) and two copies with an OR of 1.42 (95% CI 1.15-1.77), compared with no copies, under a model of multiplicative penetrance. The association with the c.454-397C --> T and c.975C --> G haplotypes was similar. Our data indicated that these haplotypes were more influential in women with a high body mass index. Adjustment for multiple comparisons rendered the associations statistically non-significant. CONCLUSION: We found suggestions of an association between common haplotypes in ESR1 and the risk for ductal breast cancer that is stronger in heavy women. 15217512 59 72 breast cancer Disease D001943 15217512 134 147 breast cancer Disease D001943 15217512 280 284 ESR1 Gene 2099 15217512 306 319 breast cancer Disease D001943 15217512 348 361 breast cancer Disease D001943 15217512 485 489 ESR1 Gene 2099 15217512 1104 1117 breast cancer Disease D001943 15217512 1292 1305 breast cancer Disease D001943 15217512 1681 1714 women with a high body mass index Environment 2099-D001943 15217512 1889 1893 ESR1 Gene 2099 15217512 1918 1931 breast cancer Disease D001943 15217512 1952 1963 heavy women Environment 2099-D001943 17827443|t|Interaction of soy food and tea consumption with CYP19A1 genetic polymorphisms in the development of endometrial cancer. 17827443|t|Certain polyphenols inhibit the activity of aromatase, a critical enzyme in estrogen synthesis that is coded by the CYP19A1 gene. Consumption of polyphenol-rich foods and beverages, thus, may interact with CYP19A1 genetic polymorphisms in the development of endometrial cancer. The authors tested this hypothesis in the Shanghai Endometrial Cancer Study (1997-2003), a population-based case-control study of 1,204 endometrial cancer cases and 1,212 controls. Dietary information was obtained by use of a validated food frequency questionnaire. Genotypes of CYP19A1 at rs28566535, rs1065779, rs752760, rs700519, and rs1870050 were available for 1,042 cases and 1,035 controls. Unconditional logistic regression models were used to calculate odds ratios and their 95% confidence intervals after adjustment for potential confounding factors. Higher intake of soy foods and tea consumption were both inversely associated with the risk of endometrial cancer, with odds ratios of 0.8 (95% confidence interval: 0.6, 1.0) for the highest versus the lowest tertiles of intake of soy and 0.8 (95% confidence interval: 06, 0.9) for ever tea consumption. The association of single nucleotide polymorphisms rs1065779, rs752760, and rs1870050 with endometrial cancer was modified by tea consumption (p(interaction) < 0.05) but not by soy isoflavone intake. The authors' findings suggest that tea polyphenols may modify the effect of CYP19A1 genetic polymorphisms on the development of endometrial cancer. 17827443 28 43 tea consumption Environment 1588-D016889 17827443 49 56 CYP19A1 Gene 1588 17827443 101 119 endometrial cancer Disease D016889 17827443 116 123 CYP19A1 Gene 1588 17827443 206 213 CYP19A1 Gene 1588 17827443 258 276 endometrial cancer Disease D016889 17827443 414 432 endometrial cancer Disease D016889 17827443 557 564 CYP19A1 Gene 1588 17827443 934 952 endometrial cancer Disease D016889 17827443 1234 1252 endometrial cancer Disease D016889 17827443 1269 1284 tea consumption Environment 1588-D016889 17827443 1378 1393 tea polyphenols Environment 1588-D016889 17827443 1419 1426 CYP19A1 Gene 1588 17827443 1471 1489 endometrial cancer Disease D016889 17596594|t|Systematic evaluation of genetic variants in the inflammation pathway and risk of lung cancer. 17596594|t|Inflammatory responses to environmental exposures, such as tobacco smoke, may play a role in lung carcinogenesis. To test this hypothesis, we studied genetic polymorphisms in the inflammation pathway in relation to lung cancer risk. We evaluated a panel of 59 single nucleotide polymorphisms (SNP) in 37 inflammation-related genes among non-Hispanic Caucasian lung cancer cases (N=1,553) and controls (N=1,730) from Houston, Texas. Logistic regression was used to assess associations with lung cancer under a dominant genetic model adjusted for sex, age, and smoking. Haplotypes were estimated with the expectation-maximization algorithm. False-positive report probabilities (FPRP) were calculated for significant associations. Interleukin 1 beta (IL1B) C3954T was associated with lung cancer [odds ratio (OR), 1.27; 95% confidence interval (95% CI), 1.10-1.47; FPRP 0.148]. Two IL1A SNPs (C-889T and Ala(114)Ser) were also related to lung cancer (OR, 1.18-1.22), although FPRPs were higher. One IL1A-IL1B haplotype, containing only the IL1B 3954T allele, was associated with elevated lung cancer risk (OR, 1.80; 95% CI, 1.24-2.61). These associations were stronger in heavy smokers, particularly for IL1B C3954T (OR, 1.59; 95% CI, 1.28-1.97; FPRP 0.004). Lung cancer risk was unrelated to polymorphisms in IL1 receptor or antagonist genes. Associations with lung cancer were also seen for SNPs in granulocyte macrophage colony stimulating factor and peroxisome proliferator-activated factor-delta, but FPRPs were high. IL1A and IL1B polymorphisms are associated with increased lung cancer risk, especially among heavy smokers. IL1A and IL1B are critical signals in initiating inflammation. Our results suggest that a dysregulated inflammatory response to tobacco-induced lung damage promotes carcinogenesis. 17596594 49 61 inflammation Disease D007249 17596594 82 93 lung cancer Disease D008175 17596594 98 112 carcinogenesis Disease D063646 17596594 179 191 inflammation Disease D007249 17596594 215 226 lung cancer Disease D008175 17596594 304 316 inflammation Disease D007249 17596594 360 371 lung cancer Disease D008175 17596594 489 500 lung cancer Disease D008175 17596594 728 746 Interleukin 1 beta Gene 3553 17596594 748 752 IL1B Gene 3553 17596594 781 792 lung cancer Disease D008175 17596594 879 883 IL1A Gene 3552 17596594 935 946 lung cancer Disease D008175 17596594 996 1000 IL1A Gene 3552 17596594 1001 1005 IL1B Gene 3553 17596594 1037 1041 IL1B Gene 3553 17596594 1085 1096 lung cancer Disease D008175 17596594 1169 1182 heavy smokers Environment 3552-D008175 17596594 1169 1182 heavy smokers Environment 3553-D008175 17596594 1201 1205 IL1B Gene 3553 17596594 1256 1267 Lung cancer Disease D008175 17596594 1359 1370 lung cancer Disease D008175 17596594 1520 1524 IL1A Gene 3552 17596594 1529 1533 IL1B Gene 3553 17596594 1578 1589 lung cancer Disease D008175 17596594 1613 1626 heavy smokers Environment 3552-D008175 17596594 1613 1626 heavy smokers Environment 3553-D008175 17596594 1628 1632 IL1A Gene 3552 17596594 1637 1641 IL1B Gene 3553 17596594 1677 1689 inflammation Disease D007249 17596594 1772 1783 lung damage Disease D055370 17596594 1793 1807 carcinogenesis Disease D063646 18281250|t|Estrogen-biosynthesis gene CYP17 and its interactions with reproductive, hormonal and lifestyle factors in breast cancer risk: results from the Long Island Breast Cancer Study Project. 18281250|t|The genes that are involved in estrogen biosynthesis, cellular binding and metabolism may contribute to breast cancer susceptibility. We examined the effect of the CYP17 promoter T --> C polymorphism and its interactions with the reproductive history, exogenous hormone use and selected lifestyle risk factors on breast cancer risk among 1037 population-based incident cases and 1096 population-based controls in the Long Island Breast Cancer Study Project. Overall, there were no associations between the CYP17 genotype and breast cancer risk. Among postmenopausal women, the joint exposure to higher body mass index (BMI) and the variant C allele was associated with an increased risk of breast cancer [odds ratio (OR), 1.60; 95% confidence interval (CI), 1.15-2.22]. The joint exposure to the variant C allele and long-term use of hormone replacement therapy (HRT) (>51 months) was related to an increased risk of breast cancer (OR, 1.51; 95% CI, 0.99-2.31) especially estrogen receptor-positive, progesterone receptor-positive breast cancer (OR, 1.87; 95% CI, 1.08-3.25). Among the control population, the CYP17 variant C allele was inversely associated with long-term use of postmenopausal HRT and a higher BMI in postmenopausal women. In conclusion, the findings suggest that the CYP17 variant C allele may increase breast cancer risk in conjunction with long-term HRT use and high BMI in postmenopausal women. 18281250 27 32 CYP17 Gene 1586 18281250 59 103 reproductive, hormonal and lifestyle factors Environment 1586-D001943 18281250 107 120 breast cancer Disease D001943 18281250 104 117 breast cancer Disease D001943 18281250 164 169 CYP17 Gene 1586 18281250 313 326 breast cancer Disease D001943 18281250 506 511 CYP17 Gene 1586 18281250 525 538 breast cancer Disease D001943 18281250 595 623 higher body mass index (BMI) Environment 1586-D001943 18281250 690 703 breast cancer Disease D001943 18281250 817 867 long-term use of hormone replacement therapy (HRT) Environment 1586-D001943 18281250 917 930 breast cancer Disease D001943 18281250 1000 1021 progesterone receptor Gene 5241 18281250 1031 1044 breast cancer Disease D001943 18281250 1110 1115 CYP17 Gene 1586 18281250 1163 1198 long-term use of postmenopausal HRT Environment 1586-D001943 18281250 1203 1215 a higher BMI Environment 1586-D001943 18281250 1286 1291 CYP17 Gene 1586 18281250 1322 1335 breast cancer Disease D001943 18281250 1361 1378 long-term HRT use Environment 1586-D001943 18281250 1383 1391 high BMI Environment 1586-D001943 20061204|t|Genetic polymorphism of glutathione S-transferase T1 and the risk of colorectal cancer: a meta-analysis. 20061204|t|BACKGROUND: Studies investigating the association between genetic polymorphism of glutathione S-transferase T1 (GSTT1) and risk of colorectal cancer have reported conflicting results. In order to clarify the effect of GSTT1 polymorphism on the risk of developing colorectal cancer, we carried out a meta-analysis using published data to obtain more precise estimates of risk. METHODS: Electronic searches of PubMed and EMBASE were conducted to select studies for this meta-analysis. Papers were included if they were observational studies investigating the association between GSTT1 polymorphism and colorectal cancer risk. The principal outcome measure was the odds ratio (OR) with 95% confidence interval (CI) for the risk of colorectal cancer associated with GSTT1 null genotype. RESULTS: We identified 30 eligible studies, which included 7635 cases and 12,911 controls. The combined results based on all studies showed that there was a statistically significant link between GSTT1 null genotype and colorectal cancer risk (OR=1.20, 95% CI=1.03-1.40). In the analysis of ethnic groups, we observed distinct differences associated with GSTT1 null genotype, the pooled odds ratios for the GSTT1 polymorphism were 1.32 in Caucasians (95% CI=1.09-1.58) and 1.03 in Asians (95% CI=0.81-1.32). As far as concerned the interaction between GSTT1 genotype and colorectal cancer risk in relation to smoking history, there was no increase in risk for smokers or nonsmokers with the GSTT1 null genotype (smokers: OR=1.13, 95% CI=0.80-1.60, nonsmokers: OR=0.99, 95% CI=0.71-1.38). When stratifying by the location of colorectal cancer, we found that there was a statistically significant link in rectal cancer (OR=1.50, 95% CI=1.09-2.07), but not in colon cancer (OR=1.33, 95% CI=0.94-1.88). No associations could be detected between null GSTT1 polymorphism and age, sex, tumor stage and differentiation. CONCLUSION: Our current study demonstrates that GSTT1 null genotype is associated with an increased risk of colorectal cancer, specifically, among Caucasians. 20061204 24 52 glutathione S-transferase T1 Gene 2952 20061204 69 86 colorectal cancer Disease D015179 20061204 82 110 glutathione S-transferase T1 Gene 2952 20061204 112 117 GSTT1 Gene 2952 20061204 131 148 colorectal cancer Disease D015179 20061204 218 223 GSTT1 Gene 2952 20061204 263 280 colorectal cancer Disease D015179 20061204 577 582 GSTT1 Gene 2952 20061204 600 617 colorectal cancer Disease D015179 20061204 728 745 colorectal cancer Disease D015179 20061204 762 767 GSTT1 Gene 2952 20061204 979 984 GSTT1 Gene 2952 20061204 1003 1020 colorectal cancer Disease D015179 20061204 1138 1143 GSTT1 Gene 2952 20061204 1190 1195 GSTT1 Gene 2952 20061204 1222 1232 Caucasians Environment 2952-D015179 20061204 1335 1340 GSTT1 Gene 2952 20061204 1354 1371 colorectal cancer Disease D015179 20061204 1474 1479 GSTT1 Gene 2952 20061204 1607 1624 colorectal cancer Disease D015179 20061204 1686 1699 rectal cancer Environment 2952-D015179 20061204 1693 1699 cancer Disease D009369 20061204 1740 1752 colon cancer Disease D003110 20061204 1829 1834 GSTT1 Gene 2952 20061204 1862 1867 tumor Disease D009369 20061204 1943 1948 GSTT1 Gene 2952 20061204 2003 2020 colorectal cancer Disease D015179 20061204 2042 2052 Caucasians Environment 2952-D015179 27186328|t|Genes, environment and gene expression in colon tissue: a pathway approach to determining functionality. 27186328|t|Genetic and environmental factors have been shown to work together to alter cancer risk. In this study we evaluate previously identified gene and lifestyle interactions in a candidate pathway that were associated with colon cancer risk to see if these interactions altered gene expression. We analyzed non-tumor RNA-seq data from 144 colon cancer patients who had genotype, recent cigarette smoking, diet, body mass index (BMI), and recent aspirin/non-steroidal anti-inflammatory use data. Using a false discovery rate of 0.1, we evaluated differential gene expression between high and low levels of lifestyle exposure and genotypes using DESeq2. Thirteen pathway genes and 17 SNPs within those genes were associated with altered expression of other genes in the pathway. BMI, NSAIDs use and dietary components of the oxidative balance score (OBS) also were associated with altered gene expression. SNPs previously identified as interacting with these lifestyle factors, altered expression of pathway genes. NSAIDs interacted with 10 genes (15 SNPs) within those genes to alter expression of 28 pathway genes; recent cigarette smoking interacted with seven genes (nine SNPs) to alter expression of 27 genes. BMI interacted with FLT1, KDR, SEPN1, TERT, TXNRD2, and VEGFA to alter expression of eight genes. Three genes (five SNPs) interacted with OBS to alter expression of 12 genes. These data provide support for previously identified lifestyle and gene interactions associated with colon cancer in that they altered expression of key pathway genes. The need to consider lifestyle factors in conjunction with genetic factors is illustrated. 27186328 76 82 cancer Disease D009369 27186328 218 230 colon cancer Disease D003110 27186328 306 311 tumor Disease D009369 27186328 334 346 colon cancer Disease D003110 27186328 1208 1211 BMI Environment 57190-D003110 27186328 1208 1211 BMI Environment 2321-D003110 27186328 1208 1211 BMI Environment 3791-D003110 27186328 1208 1211 BMI Environment 7015-D003110 27186328 1208 1211 BMI Environment 10587-D003110 27186328 1208 1211 BMI Environment 7422-D003110 27186328 1228 1232 FLT1 Gene 2321 27186328 1234 1237 KDR Gene 3791 27186328 1239 1244 SEPN1 Gene 57190 27186328 1246 1250 TERT Gene 7015 27186328 1252 1258 TXNRD2 Gene 10587 27186328 1264 1269 VEGFA Gene 7422 27186328 1436 1445 lifestyle Environment 57190-D003110 27186328 1436 1445 lifestyle Environment 2321-D003110 27186328 1436 1445 lifestyle Environment 3791-D003110 27186328 1436 1445 lifestyle Environment 7015-D003110 27186328 1436 1445 lifestyle Environment 10587-D003110 27186328 1436 1445 lifestyle Environment 7422-D003110 27186328 1484 1496 colon cancer Disease D003110 20937634|t|Cigarette smoking, genetic variants in carcinogen-metabolizing enzymes, and colorectal cancer risk. 20937634|t|The risk of colorectal cancer associated with smoking is unclear and may be influenced by genetic variation in enzymes that metabolize cigarette carcinogens. The authors examined the colorectal cancer risk associated with smoking and 26 variants in carcinogen metabolism genes in 1,174 colorectal cancer cases and 1,293 population-based controls recruited in Canada by the Ontario Familial Colorectal Cancer Registry from 1997 to 2001. Adjusted odds ratios were calculated by multivariable logistic regression. Smoking for >27 years was associated with a statistically significant increased colorectal cancer risk (adjusted odds ratio (AOR) = 1.25, 95% confidence interval (CI): 1.02, 1.53) in all subjects. Colorectal cancer risk associated with smoking was higher in males for smoking status, duration, and intensity. The CYP1A1-3801-CC (AOR = 0.47, 95% CI: 0.23, 0.94) and CYP2C9-430-CT (AOR = 0.82, 95% CI: 0.68, 0.99) genotypes were associated with decreased risk, and the GSTM1-K173N-CG (AOR = 1.99, 95% CI: 1.21, 3.25) genotype was associated with an increased risk of colorectal cancer. Statistical interactions between smoking and genetic variants were assessed by comparing logistic regression models with and without a multiplicative interaction term. Significant interactions were observed between smoking status and SULT1A1-638 (P = 0.02), NAT2-857 (P = 0.01), and CYP1B1-4390 (P = 0.04) variants and between smoking duration and NAT1-1088 (P = 0.02), SULT1A1-638 (P = 0.04), and NAT1-acetylator (P = 0.03) status. These findings support the hypothesis that prolonged cigarette smoking is associated with increased risk of colorectal cancer and that this risk may be modified by variation in carcinogen metabolism genes. 20937634 76 93 colorectal cancer Disease D015179 20937634 12 29 colorectal cancer Disease D015179 20937634 183 200 colorectal cancer Disease D015179 20937634 286 303 colorectal cancer Disease D015179 20937634 390 407 Colorectal Cancer Disease D015179 20937634 591 608 colorectal cancer Disease D015179 20937634 708 725 Colorectal cancer Disease D015179 20937634 824 830 CYP1A1 Gene 1543 20937634 876 882 CYP2C9 Gene 1559 20937634 978 983 GSTM1 Gene 2944 20937634 1076 1093 colorectal cancer Disease D015179 20937634 1310 1324 smoking status Environment 1545-D15179 20937634 1310 1324 smoking status Environment 6817-D015179 20937634 1329 1336 SULT1A1 Gene 6817 20937634 1378 1384 CYP1B1 Gene 1545 20937634 1422 1438 smoking duration Environment 9-D15179 20937634 1422 1438 smoking duration Environment 6817-D015179 20937634 1443 1447 NAT1 Gene 9 20937634 1465 1472 SULT1A1 Gene 6817 20937634 1493 1497 NAT1 Gene 9 20937634 1571 1598 prolonged cigarette smoking Environment 9-D15179 20937634 1571 1598 prolonged cigarette smoking Environment 1545-D15179 20937634 1571 1598 prolonged cigarette smoking Environment 6817-D015179 20937634 1636 1653 colorectal cancer Disease D015179 18496222|t|Meta-analysis and pooled analysis of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers: a HuGE-GSEC review. 18496222|t|The association of GSTM1 and CYP1A1 polymorphisms and oral and pharyngeal cancers was assessed through a meta-analysis of published case-control studies and a pooled analysis of both published and unpublished case-control studies from the Genetic Susceptibility to Environmental Carcinogens database (http://www.upci.upmc.edu/research/ccps/ccontrol/index.html ). Thirty publications used in the meta-analysis included a total of 7783 subjects (3177 cases and 4606 controls); 21 datasets, 9397 subjects (3130 cases and 6267 controls) were included in the pooled analysis. The GSTM1 deletion was 2-fold more likely to occur in African American and African cases than controls (odds ratio: 1.7, 95% confidence interval: 0.9-3.3), although this was not observed among whites (odds ratio: 1.0, 95% confidence interval: 0.9-1.1). The meta-analysis and pooled analysis showed a significant association between oral and pharyngeal cancer and the CYP1A1 MspI homozygous variant (meta-ORm2/m2: 1.9, 95% confidence interval: 1.4-2.7; Pooled ORm2m2: 2.0, 95% confidence interval: 1.3-3.1; ORm1m2 or [infi]m2m2: 1.3, 95% confidence interval: 1.1-1.6). The association was present for the CYP1A1 (exon 7) polymorphism (ORVal/Val: 2.2, 95% confidence interval: 1.1-4.5) in ever smokers. A joint effect was observed for GSTM1 homozygous deletion and the CYP1A1 m1m2 variant on cancer risk. Our findings suggest that tobacco use and genetic factors play a significant role in oral and pharyngeal cancer. 18496222 37 42 GSTM1 Gene 2944 18496222 47 53 CYP1A1 Gene 1543 18496222 81 99 pharyngeal cancers Disease D010610 18496222 19 24 GSTM1 Gene 2944 18496222 29 35 CYP1A1 Gene 1543 18496222 63 81 pharyngeal cancers Disease D010610 18496222 239 261 Genetic Susceptibility Disease D020022 18496222 575 580 GSTM1 Gene 2944 18496222 923 929 cancer Disease D009369 18496222 938 944 CYP1A1 Gene 1543 18496222 975 979 ORm2 Gene 5005 18496222 1175 1181 CYP1A1 Gene 1543 18496222 1258 1270 ever smokers Environment 1543-D009369 18496222 1304 1309 GSTM1 Gene 2944 18496222 1338 1344 CYP1A1 Gene 1543 18496222 1361 1367 cancer Disease D009369 18496222 1400 1411 tobacco use Environment 1543-D009369 18496222 1479 1485 cancer Disease D009369 19944409|t|The risk of posttraumatic stress disorder after trauma depends on traumatic load and the catechol-o-methyltransferase Val(158)Met polymorphism. 19944409|t|BACKGROUND: The risk for posttraumatic stress disorder (PTSD) depends on the number of traumatic event types experienced in a dose-response relationship, but genetic factors are known to also influence the risk of PTSD. The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been found to affect fear extinction and might play a role in the etiology of anxiety disorders. METHODS: Traumatic load and lifetime and current diagnosis of PTSD and COMT genotype were assessed in a sample of 424 survivors of the Rwandan Genocide living in the Nakivale refugee camp in southwestern Uganda. RESULTS: Higher numbers of different lifetime traumatic event types led to a higher prevalence of lifetime PTSD in a dose-response relationship. However, this effect was modulated by the COMT genotype: whereas Val allele carriers showed the typical dose-response relationship, Met/Met homozygotes exhibited a high risk for PTSD independently of the severity of traumatic load. CONCLUSIONS: The present findings indicate a gene-environment interaction between the human COMT Val158Met polymorphism and the number of traumatic event types experienced in the risk of developing PTSD. 19944409 12 41 posttraumatic stress disorder Disease D013313 19944409 48 54 trauma Disease D014947 19944409 48 54 trauma Environment 1312-D013313 19944409 66 75 traumatic Disease D014947 19944409 89 117 catechol-o-methyltransferase Gene 1312 19944409 25 54 posttraumatic stress disorder Disease D013313 19944409 56 60 PTSD Disease D013313 19944409 87 96 traumatic Disease D014947 19944409 214 218 PTSD Disease D013313 19944409 224 252 catechol-O-methyltransferase Gene 1312 19944409 254 258 COMT Gene 1312 19944409 365 382 anxiety disorders Disease D001008 19944409 393 402 Traumatic Disease D014947 19944409 446 450 PTSD Disease D013313 19944409 455 459 COMT Gene 1312 19944409 605 651 Higher numbers of different lifetime traumatic Environment 1312-D013313 19944409 642 651 traumatic Disease D014947 19944409 703 707 PTSD Disease D013313 19944409 783 787 COMT Gene 1312 19944409 919 923 PTSD Disease D013313 19944409 957 966 traumatic Disease D014947 19944409 1065 1069 COMT Gene 1312 19944409 1097 1120 the number of traumatic Environment 1312-D013313 19944409 1111 1120 traumatic Disease D014947 19944409 1171 1175 PTSD Disease D013313 20554746|t|A functional variant (-1304T>G) in the MKK4 promoter contributes to a decreased risk of lung cancer by increasing the promoter activity. 20554746|t|Mitogen-activated protein kinase kinase 4 (MKK4) is a critical mediator of stress-activated protein kinase signals that regulate apoptosis, inflammations and tumorigenesis. Several polymorphisms have been identified in the MKK4 gene. We hypothesized that genetic variants in the MKK4 promoter may alter its expression and thus cancer risk. In a case-control study of 1056 lung cancer cases and 1056 sex and age frequency-matched cancer-free controls, we genotyped two common polymorphisms in the MKK4 promoter region (-1304T>G and -1044A>T) with the Taqman assay, and we found that compared with the most common -1304TT genotype, carriers of -1304G variant genotypes had a decreased risk of lung cancer [odds ratio (OR) = 0.74; 95% confidence interval (CI) = 0.61-0.90 for TG, and OR = 0.62; 95% CI = 0.41-0.94 for GG] in an allele dose-response manner (adjusted P(trend) = 0.0005). Further stratification analysis showed that the protective role of the -1304G variant allele was more evident in low or normal body mass index (BMI) but restrained in the overweighters and that the -1304G variant genotypes interacted with BMI in reducing cancer risk (adjusted P(interaction) = 0.003). Moreover, the luciferase assay showed that the G allele in the promoter significantly increased the transcription activity of the MKK4 gene in vitro and that the MKK4 protein expression levels of the G variant carriers was significantly higher in tumor tissues than those of the -1304TT genotype. However, no significant association was observed between the -1044A>T polymorphism and risk of lung cancer. Our data suggest that the functional -1304G variant in the MKK4 promoter contributes to a decreased risk of lung cancer by increasing the promoter activity and that the G variant may be a marker for susceptibility to lung cancer. 20554746 39 43 MKK4 Gene 6416 20554746 88 99 lung cancer Disease D008175 20554746 0 41 Mitogen-activated protein kinase kinase 4 Gene 6416 20554746 43 47 MKK4 Gene 6416 20554746 140 153 inflammations Disease D007249 20554746 158 171 tumorigenesis Disease D063646 20554746 223 227 MKK4 Gene 6416 20554746 279 283 MKK4 Gene 6416 20554746 327 333 cancer Disease D009369 20554746 372 383 lung cancer Disease D008175 20554746 429 435 cancer Disease D009369 20554746 496 500 MKK4 Gene 6416 20554746 691 702 lung cancer Disease D008175 20554746 996 1031 low or normal body mass index (BMI) Environment 6416-D009369 20554746 996 1031 low or normal body mass index (BMI) Environment 6416-D008175 20554746 1054 1067 overweighters Environment 6416-D009369 20554746 1054 1067 overweighters Environment 6416-D008175 20554746 1122 1125 BMI Environment 6416-D009369 20554746 1122 1125 BMI Environment 6416-D008175 20554746 1138 1144 cancer Disease D009369 20554746 1315 1319 MKK4 Gene 6416 20554746 1347 1351 MKK4 Gene 6416 20554746 1432 1437 tumor Disease D009369 20554746 1577 1588 lung cancer Disease D008175 20554746 1649 1653 MKK4 Gene 6416 20554746 1698 1709 lung cancer Disease D008175 20554746 1807 1818 lung cancer Disease D008175 20336806|t|Gender differences in the genetic and environmental determinants of adolescent depression. 20336806|t|BACKGROUND: The well-documented gender differences in the risk for depression may be explained by genetic factors, by different responses to social context, or by a combination of both. We sought to assess whether there were gender differences in the longitudinal associations between serotonin transporter promoter (5-HTTLPR) genotype and depressive symptoms in adolescents, and whether macrosocial context plays a role in explaining any observed differences. METHODS: Using data from a nationally representative survey of adolescents, we applied multilevel mixed models to assess, separately for adolescent males and females (a) the relation between 5-HTTLPR genotype and depressive symptoms and (b) the interaction of county-level deprivation and 5-HTTLPR genotype in models predicting depressive symptoms. All models adjusted for age and other covariates. RESULTS: Among females (n=560), main effects models showed an association between the sl genotype and lowered risk of depressive symptoms (b=-.18, P=.03). Among males (n=524), interaction models showed an association between sl genotype and lowered risk of depressive symptoms in deprived counties only (b=-.32, P=.04). CONCLUSIONS: In adolescent females, the 5-HTTLPR sl genotype confers protection against depressive symptoms independent of county-level social context, whereas in adolescent males, protection by the same genotype is conferred only within the context of county-level deprivation. Future work should aim to understand how genetic and macrosocial factors jointly shape risk for mental illness, and how these factors shape gender differences in mental illness. 20336806 79 89 depression Disease D003866 20336806 67 77 depression Disease D003866 20336806 317 325 5-HTTLPR Gene 6532 20336806 340 359 depressive symptoms Disease D003866 20336806 652 660 5-HTTLPR Gene 6532 20336806 674 693 depressive symptoms Disease D003866 20336806 750 758 5-HTTLPR Gene 6532 20336806 789 808 depressive symptoms Disease D003866 20336806 978 997 depressive symptoms Disease D003866 20336806 1117 1136 depressive symptoms Disease D003866 20336806 1140 1157 deprived counties Environment 6532-D003866 20336806 1220 1228 5-HTTLPR Gene 6532 20336806 1268 1287 depressive symptoms Disease D003866 20336806 1433 1457 county-level deprivation Environment 6532-D003866 20336806 1555 1569 mental illness Disease 1 20336806 1621 1635 mental illness Disease 1 17066444|t|Association of frequent consumption of fatty fish with prostate cancer risk is modified by COX-2 polymorphism. 17066444|t|Dietary intake of marine fatty acids from fish may protect against prostate cancer development. We studied this association and whether it is modified by genetic variation in cyclooxygenase (COX)-2, a key enzyme in fatty acid metabolism and inflammation. We assessed dietary intake of fish among 1,499 incident prostate cancer cases and 1,130 population controls in Sweden. Five single nucleotide polymorphisms (SNPs) were identified and genotyped in available blood samples for 1,378 cases and 782 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multivariate logistic regression. Multiplicative and additive interactions between fish intake and COX-2 SNPs on prostate cancer risk were evaluated. Eating fatty fish (e.g., salmon-type fish) once or more per week, compared to never, was associated with reduced risk of prostate cancer (OR: 0.57, 95% CI: 0.43-0.76). The OR comparing the highest to the lowest quartile of marine fatty acids intake was 0.70 (95% CI: 0.51-0.97). We found a significant interaction (p < 0.001) between salmon-type fish intake and a SNP in the COX-2 gene (rs5275: +6365 T/C), but not with the 4 other SNPs examined. We found strong inverse associations with increasing intake of salmon-type fish among carriers of the variant allele (OR for once per week or more vs. never = 0.28, 95% CI: 0.18-0.45; p(trend) < 0.01), but no association among carriers of the more common allele. Frequent consumption of fatty fish and marine fatty acids appears to reduce the risk of prostate cancer, and this association is modified by genetic variation in the COX-2 gene. 17066444 15 49 frequent consumption of fatty fish Environment 4513-D011471 17066444 55 70 prostate cancer Disease D011471 17066444 91 96 COX-2 Gene 4513 17066444 67 82 prostate cancer Disease D011471 17066444 175 197 cyclooxygenase (COX)-2 Gene 4513 17066444 241 253 inflammation Disease D007249 17066444 311 326 prostate cancer Disease D011471 17066444 677 682 COX-2 Gene 4513 17066444 691 706 prostate cancer Disease D011471 17066444 849 864 prostate cancer Disease D011471 17066444 1103 1108 COX-2 Gene 4513 17066444 1438 1495 Frequent consumption of fatty fish and marine fatty acids Environment 4513-D011471 17066444 1526 1541 prostate cancer Disease D011471 17066444 1604 1609 COX-2 Gene 4513 18768514|t|Talc use, variants of the GSTM1, GSTT1, and NAT2 genes, and risk of epithelial ovarian cancer. 18768514|t|Epidemiologic evidence suggests a possible association between genital use of talcum powder and risk of epithelial ovarian cancer; however, the biological basis for this association is not clear. We analyzed interactions between talc use and genes in detoxification pathways [glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), and N-acetyltransferase 2 (NAT2)] to assess whether the talc/ovarian cancer association is modified by variants of genes potentially involved in the response to talc. Our analysis included 1,175 cases and 1,202 controls from a New England-based case-control study and 210 cases and 600 controls from the prospective Nurses' Health Study. We genotyped participants for the GSTM1 and GSTT1 gene deletions and three NAT2 polymorphisms. We used logistic regression to analyze the main effect of talc use, genotype, and gene-talc interactions in each population and pooled the estimates using a random-effects model. Regular talc use was associated with increased ovarian cancer risk in the combined study population (RR, 1.36; 95% CI, 1.14-1.63; P(trend) < 0.001). Independent of talc, the genes examined were not clearly associated with risk. However, the talc/ovarian cancer association varied by GSTT1 genotype and combined GSTM1/GSTT1 genotype. In the pooled analysis, the association with talc was stronger among women with the GSTT1-null genotype (P(interaction) = 0.03), particularly in combination with the GSTM1-present genotype (P(interaction) = 0.03). There was no clear evidence of an interaction with GSTM1 alone or NAT2. These results suggest that women with certain genetic variants may have a higher risk of ovarian cancer associated with genital talc use. Additional research is needed on these interactions and the underlying biological mechanisms. 18768514 26 31 GSTM1 Gene 2944 18768514 33 38 GSTT1 Gene 2952 18768514 44 48 NAT2 Gene 10 18768514 68 93 epithelial ovarian cancer Disease C538090 18768514 104 129 epithelial ovarian cancer Disease C538090 18768514 276 304 glutathione S-transferase M1 Gene 2944 18768514 306 311 GSTM1 Gene 2944 18768514 314 342 glutathione S-transferase T1 Gene 2952 18768514 344 349 GSTT1 Gene 2952 18768514 356 377 N-acetyltransferase 2 Gene 10 18768514 379 383 NAT2 Gene 10 18768514 413 427 ovarian cancer Disease D010051 18768514 724 729 GSTM1 Gene 2944 18768514 734 739 GSTT1 Gene 2952 18768514 765 769 NAT2 Gene 10 18768514 1011 1025 ovarian cancer Disease D010051 18768514 1205 1209 talc Environment 2952-D010051 18768514 1205 1209 talc Environment 2952-C538090 18768514 1210 1224 ovarian cancer Disease D010051 18768514 1247 1252 GSTT1 Gene 2952 18768514 1275 1280 GSTM1 Gene 2944 18768514 1281 1286 GSTT1 Gene 2952 18768514 1342 1346 talc Environment 2952-D010051 18768514 1342 1346 talc Environment 2952-C538090 18768514 1381 1386 GSTT1 Gene 2952 18768514 1463 1468 GSTM1 Gene 2944 18768514 1562 1567 GSTM1 Gene 2944 18768514 1577 1581 NAT2 Gene 10 18768514 1672 1686 ovarian cancer Disease D010051 18768514 1703 1719 genital talc use Environment 2952-D010051 18768514 1703 1719 genital talc use Environment 2952-C538090 15734977|t|Gene-smoking interaction associations for the ERCC1 polymorphisms in the risk of lung cancer. 15734977|t|Cigarette smoking may induce DNA damage. Lower DNA repair capacities have been associated with higher risk of lung cancer. Excision repair cross-complementing group 1 (ERCC1) is the lead enzyme in the nucleotide excision repair process, and low expression of ERCC1 mRNA levels has been associated with higher risk of cancers. We examined the association between two polymorphisms of ERCC1, 8092C > A (rs3212986) and 19007T > C (codon 118, rs11615), which are associated with altered ERCC1 mRNA stability and mRNA levels, in 1,752 Caucasian lung cancer patients and 1,358 controls. The results were analyzed using logistic regression models, adjusting for relevant covariates. The two polymorphisms were in Hardy-Weinberg disequilibrium and in linkage disequilibrium. There was no overall association between ERCC1 polymorphisms and lung cancer risk, with the adjusted odds ratios (AOR) of 1.26 [95% confidence interval (95% CI), 0.81-1.96] for the 8092C > A polymorphism (A/A versus C/C) and 0.93 (95% CI, 0.67-1.30) for the 19007T > C polymorphism (C/C versus T/T). Stratified analyses revealed that the AORs for the 8092C > A polymorphism (A/A versus C/C) decreased significantly as pack-years increased, with the AOR of 2.11 (95% CI, 1.03-4.31) in never smokers and 0.50 (95% CI, 0.25-1.01) in heavy smokers (>/=56 pack-years), respectively. Consistent results were found when gene-smoking interaction was incorporated by joint effects and interactions models that considered both discrete and continuous variables for cumulative smoking exposure. The same direction for the gene-smoking interaction was found for the 19007T > C polymorphism, although the interaction was not statistically significant. In conclusion, ERCC1 8092C > A polymorphism may modify the associations between cumulative cigarette smoking and lung cancer risk. 15734977 5 12 smoking Environment 2067-D008175 15734977 46 51 ERCC1 Gene 2067 15734977 81 92 lung cancer Disease D008175 15734977 110 121 lung cancer Disease D008175 15734977 123 166 Excision repair cross-complementing group 1 Gene 2067 15734977 168 173 ERCC1 Gene 2067 15734977 259 264 ERCC1 Gene 2067 15734977 317 324 cancers Disease D009369 15734977 383 388 ERCC1 Gene 2067 15734977 483 488 ERCC1 Gene 2067 15734977 540 551 lung cancer Disease D008175 15734977 808 813 ERCC1 Gene 2067 15734977 832 843 lung cancer Disease D008175 15734977 1185 1205 pack-years increased Environment 2067-D008175 15734977 1251 1264 never smokers Environment 2067-D008175 15734977 1297 1329 heavy smokers (>/=56 pack-years) Environment 2067-D008175 15734977 1385 1392 smoking Environment 2067-D008175 15734977 1479 1549 both discrete and continuous variables for cumulative smoking exposure Environment 2067-D008175 15734977 1721 1726 ERCC1 Gene 2067 15734977 1786 1814 cumulative cigarette smoking Environment 2067-D008175 15734977 1819 1830 lung cancer Disease D008175 16399771|t|Polymorphisms in nucleotide excision repair genes, smoking and breast cancer in African Americans and whites: a population-based case-control study. 16399771|t|Polymorphisms exist in several genes involved in nucleotide excision repair (NER), the principal pathway for removal of smoking-induced DNA damage. An epidemiologic study was conducted to determine whether these polymorphisms modify the association between smoking and breast cancer. DNA samples and exposure histories were analyzed as part of a large population-based case-control study of breast cancer in North Carolina. The study population included 2311 cases (894 African Americans, 1417 whites) and 2022 controls (788 African Americans, 1234 whites). Odds ratios (ORs) were calculated for breast cancer and smoking, and for breast cancer and nine non-synonymous coding polymorphisms in six NER genes (XPD codons 312 and 751, RAD23B codon 249, XPG codon 1104, XPC codon 939, XPF codons 415 and 662, and ERCC6 codons 1213 and 1230). Modification of ORs for smoking by single and combined NER genotypes was investigated. In this study population, smoking was more strongly associated with breast cancer in African American women compared with white women. Among African American women, the association of breast cancer and smoking was strongest among women with specific combinations of NER genotypes. Evidence for multiplicative interaction was found between combined NER genotypes and smoking dose (likelihood ratio test P = 0.06), duration (P = 0.09), time since cessation (P = 0.02), age at initiation (P = 0.04) and former smoking (P = 0.03). No interactions were observed in white women. Therefore, polymorphisms in NER genes may modify the relationship between breast cancer and smoking. These results are consistent with previous evidence of exposure-specific p53 mutations in breast tumors from current and former smokers, suggesting that smoking may play a role in breast cancer etiology. 16399771 63 76 breast cancer Disease D001943 16399771 269 282 breast cancer Disease D001943 16399771 391 404 breast cancer Disease D001943 16399771 596 609 breast cancer Disease D001943 16399771 631 644 breast cancer Disease D001943 16399771 732 738 RAD23B Gene 5887 16399771 781 784 XPF Gene 2072 16399771 809 814 ERCC6 Gene 2074 16399771 993 1006 breast cancer Disease D001943 16399771 1109 1122 breast cancer Disease D001943 16399771 1127 1134 smoking Environment 2074-D001943 16399771 1127 1134 smoking Environment 5887-D001943 16399771 1127 1134 smoking Environment 2072-D001943 16399771 1291 1303 smoking dose Environment 2074-D001943 16399771 1291 1303 smoking dose Environment 5887-D001943 16399771 1291 1303 smoking dose Environment 2072-D001943 16399771 1338 1346 duration Environment 2074-D001943 16399771 1338 1346 duration Environment 5887-D001943 16399771 1338 1346 duration Environment 2072-D001943 16399771 1359 1379 time since cessation Environment 2074-D001943 16399771 1359 1379 time since cessation Environment 5887-D001943 16399771 1359 1379 time since cessation Environment 2072-D001943 16399771 1392 1409 age at initiation Environment 2074-D001943 16399771 1392 1409 age at initiation Environment 5887-D001943 16399771 1392 1409 age at initiation Environment 2072-D001943 16399771 1425 1439 former smoking Environment 2074-D001943 16399771 1425 1439 former smoking Environment 5887-D001943 16399771 1425 1439 former smoking Environment 2072-D001943 16399771 1572 1585 breast cancer Disease D001943 16399771 1590 1597 smoking Environment 2074-D001943 16399771 1590 1597 smoking Environment 5887-D001943 16399771 1590 1597 smoking Environment 2072-D001943 16399771 1672 1675 p53 Gene 7157 16399771 1689 1702 breast tumors Disease D001943 16399771 1708 1734 current and former smokers Environment 7157-D001943 16399771 1779 1792 breast cancer Disease D001943 17646272|t|Functional variant of manganese superoxide dismutase (SOD2 V16A) polymorphism is associated with prostate cancer risk in the prostate, lung, colorectal, and ovarian cancer study. 17646272|t|Superoxide dismutase (SOD) plays a key role in the detoxification of superoxide free radicals. We evaluated the association of prostate cancer with genetic polymorphisms in SOD1 (CuZn-SOD; IVS3-251A>G), SOD2 [MnSOD; Ex2+24T>C (V16A)], and SOD3 (EC-SOD; IVS1+186C>T, Ex3-631C>G, Ex3-516C>T, and Ex3-489C>T), the three main isoforms of SOD. Prostate cancer cases (n = 1,320) from the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial were frequency matched to nondiseased controls (n = 1,842) by age, race, time since initial screening, and year of blood draw. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI); stratified analysis by the level of antioxidative vitamins was also conducted. The higher activity Ala variant at SOD2 Ex2+24T>C (V16A), which has been hypothesized to suppress prostate carcinogenesis, was associated with elevation of prostate cancer risk in Caucasians (Val/Ala versus Val/Val: OR, 1.17; 95% CI, 0.97-1.42; Ala/Ala versus Val/Val: OR, 1.28; 95% CI, 1.03-1.60; P(trend) = 0.03). Stratification by quartiles of dietary and supplemental vitamin E intake (IU/d) showed risks of prostate cancer tended to be increased among SOD2 Ala allele carriers, except at the highest quartile of vitamin E intake (>222; P(interaction) = 0.06, Q1-Q3 versus Q4). The association between Ala allele and prostate cancer risk among those with lower intake of vitamin E (/=30; P = 0.031) and NIN rs10145182 in ever smokers (P = 0.01). In addition, survival analyses detected significant associations between SNPs in EIF3S10 and overall survival (P = 0.009), SNPs from five genes and survival in resected cancer cases (P < 0.05), and SNPs from two other genes (P < 0.05) and survival of locally advanced cancer cases. CONCLUSION: Common variation in genes encoding regulators of mitosis may independently influence pancreatic cancer susceptibility and survival. 20056645 61 78 pancreatic cancer Disease D010190 20056645 151 161 aneuploidy Disease D000782 20056645 166 176 polyploidy Disease D011123 20056645 201 207 cancer Disease D009369 20056645 330 347 pancreatic cancer Disease D010190 20056645 419 432 breast cancer Disease D001943 20056645 532 549 pancreatic cancer Disease D010190 20056645 599 613 adenocarcinoma Disease D000230 20056645 698 715 pancreatic cancer Disease D010190 20056645 747 764 pancreatic cancer Disease D010190 20056645 836 839 NIN Gene 51199 20056645 910 927 pancreatic cancer Disease D010190 20056645 1125 1142 pancreatic cancer Disease D010190 20056645 1193 1213 high body mass index Environment 324-D010190 20056645 1237 1240 NIN Gene 51199 20056645 1255 1267 ever smokers Environment 51199-D010190 20056645 1361 1368 EIF3S10 Gene 8661 20056645 1449 1455 cancer Disease D009369 20056645 1548 1554 cancer Disease D009369 20056645 1659 1676 pancreatic cancer Disease D010190 19763824|t|Glutathione S-transferase M1 null genotype associated with gastric cancer among Asians. 19763824|t|PURPOSE: The Glutathione S-transferases (GSTs) play multiple roles in the pathogenesis and treatment of cancer. Studies investigating the association between Glutathione S-transferase M1 (GSTM1) null genotype and gastric cancer risk report conflicting results. The purpose of this study was to quantitatively summarize the evidence for such a relationship. RESULTS: This meta-analysis included 35 studies, which included 4,505 gastric cancer cases and 9,062 controls. The combined results based on all studies showed that the GSTM1 null genotype was associated with an increased risk of gastric cancer (OR = 1.15, 95% confidence interval [CI] = 1.02, 1.29). When stratifying for race, results were similar among Asians (OR = 1.24, 95% CI = 1.07, 1.44) except Caucasians (OR = 1.04, 95% CI = 0.88, 1.24). When stratifying by the location, stage, Lauren's classification, histological differentiation, lymph node metastasis, smoking, and Helicobacter pylori infection of gastric cancer, we observed that patients with diffuse classification had a significantly higher frequency null genotype (OR = 4.80, 95% CI = 1.65,13.94) than those with intestinal classification among Caucasians. CONCLUSIONS: This meta-analysis suggests that the GSTM1 null genotype may be associated with gastric cancer among Asians. 19763824 0 28 Glutathione S-transferase M1 Gene 2944 19763824 59 73 gastric cancer Disease D013274 19763824 80 86 Asians Environment 2944-D013274 19763824 104 110 cancer Disease D009369 19763824 158 186 Glutathione S-transferase M1 Gene 2944 19763824 188 193 GSTM1 Gene 2944 19763824 213 227 gastric cancer Disease D013274 19763824 427 441 gastric cancer Disease D013274 19763824 526 531 GSTM1 Gene 2944 19763824 587 601 gastric cancer Disease D013274 19763824 712 718 Asians Environment 2944-D013274 19763824 911 921 metastasis Disease D009362 19763824 936 965 Helicobacter pylori infection Disease 1 19763824 969 983 gastric cancer Disease D013274 19763824 1233 1238 GSTM1 Gene 2944 19763824 1276 1290 gastric cancer Disease D013274 19763824 1297 1303 Asians Environment 2944-D013274 20441718|t|Association study of trauma load and SLC6A4 promoter polymorphism in posttraumatic stress disorder: evidence from survivors of the Rwandan genocide. 20441718|t|OBJECTIVE: As exposure to different types of traumatic stressors increases, the occurrence of posttraumatic stress disorder (PTSD) increases. However, because some people exhibit either surprising resilience or high vulnerability, further influencing factors have been conjectured, such as gene-environment interactions. The SLC6A4 gene, which encodes serotonin transporter, has been identified as predisposing toward differential emotional processing between genotypes of its promoter polymorphism. METHOD: We investigated 408 refugees from the Rwandan genocide and assessed lifetime exposure to traumatic events, PTSD (according to DSM-IV) status, and genotype of the SLC6A4 promoter polymorphism. The study was conducted from March 2006 to February 2007. RESULTS: The prevalence of PTSD approached 100% when traumatic exposure reached extreme levels. However, persons homozygous for the short allele of the SLC6A4 promoter polymorphism showed no dose-response relationship but were at high risk for developing PTSD after very few traumatic events. This genotype influence vanished with increasing exposure to traumatic stressors. CONCLUSION: We find evidence for a gene-environment interplay for PTSD and show that genetic influences lose importance when environmental factors cause an extremely high trauma burden to an individual. In the future, it may be important to determine whether the effectiveness of therapeutic interventions in PTSD is also modulated by the SLC6A4 genotype. 20441718 21 27 trauma Disease D014947 20441718 37 43 SLC6A4 Gene 6532 20441718 69 98 posttraumatic stress disorder Disease D013313 20441718 45 54 traumatic Disease D014947 20441718 94 123 posttraumatic stress disorder Disease D013313 20441718 125 129 PTSD Disease D013313 20441718 325 331 SLC6A4 Gene 6532 20441718 597 606 traumatic Disease D014947 20441718 615 619 PTSD Disease D013313 20441718 670 676 SLC6A4 Gene 6532 20441718 785 789 PTSD Disease D013313 20441718 811 820 traumatic Disease D014947 20441718 910 916 SLC6A4 Gene 6532 20441718 1013 1017 PTSD Disease D013313 20441718 1024 1049 very few traumatic events Environment 6532-D013313 20441718 1033 1042 traumatic Disease D014947 20441718 1112 1121 traumatic Disease D014947 20441718 1199 1203 PTSD Disease D013313 20441718 1304 1310 trauma Disease D014947 20441718 1442 1446 PTSD Disease D013313 20441718 1472 1478 SLC6A4 Gene 6532 19959686|t|Assessing tumor mutations to gain insight into base excision repair sequence polymorphisms and smoking in colon cancer. 19959686|t|DNA repair enzymes function in major pathways to reverse DNA damage, including base excision repair (BER). Missense polymorphisms in BER repair genes may contribute to differences in DNA repair capacity, specific mutations, and susceptibility to cancer in the presence of exposure to carcinogens such as cigarette smoking. In a study of 1,604 incident colon cancer cases and 1,969 matched population-based controls genotyped for BER variants OGG1 (S326C) and XRCC1 (R194W, R280H, and R399Q), we found no associations with colon cancer overall. However, a 2-fold increased risk of BRAF V600E tumor mutation was observed in current and former cigarette smokers homozygous for the OGG1 polymorphism (odds ratio, 2.2; 95% confidence interval, 1.02-4.9, recessive model); similar associations were not observed for microsatellite instability, CpG island methylator phenotype, KRAS2 mutations, or TP53 mutations. The XRCC1 R194W polymorphism was associated with a modest increased risk of TP53 tumor mutations in those who regularly smoked cigarettes (odds ratio, 1.4; 95% confidence interval, 1.02-1.9). These findings point to the importance of studying tumor mutations when examining DNA repair polymorphisms and cigarette smoke exposure to identify potentially relevant associations with colorectal cancer. 19959686 10 15 tumor Disease D009369 19959686 106 118 colon cancer Disease D003110 19959686 246 252 cancer Disease D009369 19959686 352 364 colon cancer Disease D003110 19959686 442 446 OGG1 Gene 4968 19959686 459 464 XRCC1 Gene 7515 19959686 522 534 colon cancer Disease D003110 19959686 580 584 BRAF Gene 673 19959686 591 596 tumor Disease D009369 19959686 622 658 current and former cigarette smokers Environment 4968-D003110 19959686 622 658 current and former cigarette smokers Environment 673-D003110 19959686 678 682 OGG1 Gene 4968 19959686 810 836 microsatellite instability Disease D053842 19959686 871 876 KRAS2 Gene 3845 19959686 891 895 TP53 Gene 7157 19959686 911 916 XRCC1 Gene 7515 19959686 983 987 TP53 Gene 7157 19959686 988 993 tumor Disease D009369 19959686 1013 1044 who regularly smoked cigarettes Environment 7515-D003110 19959686 1013 1044 who regularly smoked cigarettes Environment 7157-D003110 19959686 1150 1155 tumor Disease D009369 19959686 1210 1234 cigarette smoke exposure Environment 7515-D015179 19959686 1210 1234 cigarette smoke exposure Environment 4968-D015179 19959686 1210 1234 cigarette smoke exposure Environment 673-D015179 19959686 1210 1234 cigarette smoke exposure Environment 7157-D015179 19959686 1286 1303 colorectal cancer Disease D015179 21382839|t|Relation of FGFR2 genetic polymorphisms to the association between oral contraceptive use and the risk of breast cancer in Chinese women. 21382839|t|The fibroblast growth factor receptor 2 gene (FGFR2) has been associated with the risk of breast cancer in multiple ethnic populations, and its effect has been suggested to be hormone-dependent. A large, 2-stage, population-based case-control study was conducted in urban Shanghai, China, during the periods of 1996-1998 and 2002-2005. Exposure and genotyping information from 2,073 patients with breast cancer and 2,084 age-matched population controls was available for evaluation of the interactions between FGFR2 polymorphisms and exogenous estrogen exposure in the development of breast cancer. A logistic regression model was used to compute adjusted odds ratios and 95% confidence intervals. Of 20 genotyped and 25 imputed single nucleotide polymorphisms (SNPs), 22 were significantly associated with breast cancer. Three genotyped SNPs in close linkage disequilibrium, rs2303568, rs3135730, and rs1078806, and an imputed SNP of rs755793 in complete linkage disequilibrium with other 8 SNPs were observed to interact significantly with oral contraceptive (OC) use. The SNP-cancer association was evident only among OC users, and the OC use was only associated with the risk of breast cancer among carriers of these minor alleles at these loci. These findings suggest that genetic variants in FGFR2 may modify the role of OC use in causing breast cancer in Chinese women. 21382839 12 17 FGFR2 Gene 2263 21382839 67 89 oral contraceptive use Environment 2263-D001943 21382839 106 119 breast cancer Disease D001943 21382839 4 39 fibroblast growth factor receptor 2 Gene 2263 21382839 46 51 FGFR2 Gene 2263 21382839 90 103 breast cancer Disease D001943 21382839 397 410 breast cancer Disease D001943 21382839 510 515 FGFR2 Gene 2263 21382839 584 597 breast cancer Disease D001943 21382839 807 820 breast cancer Disease D001943 21382839 1042 1069 oral contraceptive (OC) use Environment 2263-D001943 21382839 1079 1085 cancer Disease D009369 21382839 1121 1129 OC users Environment 2263-D001943 21382839 1135 1145 the OC use Environment 2263-D001943 21382839 1183 1196 breast cancer Disease D001943 21382839 1298 1303 FGFR2 Gene 2263 21382839 1327 1333 OC use Environment 2263-D001943 21382839 1345 1358 breast cancer Disease D001943 18349273|t|UGT1A1 genetic polymorphisms, endogenous estrogen exposure, soy food intake, and endometrial cancer risk. 18349273|t|Estrogen exposures play a critical role in the development of endometrial cancer. Genetic variation in the estrogen metabolism UGT1A1 gene may modify the effect of estrogenic exposures on endometrial cancer risk. We tested this hypothesis in a population-based case-control study of 1,047 endometrial cancer cases and 1,035 controls who completed an in-person interview and were genotyped for the UGT1A1 polymorphisms rs2070959 (A/G), rs887829 (G/A), and rs8175347 (6/7 TA repeats). Estrogen exposure-related factors evaluated include menstrual characteristics, oral contraceptive use, body mass index, waist-hip ratio, and soy food intake. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. The homozygote variant genotype (G/G) of the rs2070959 polymorphism was significantly associated with a reduced risk of endometrial cancer (odds ratio, 0.5; 95% confidence interval, 0.3-0.8). No significant associations between endometrial cancer risk and genotype were seen for the rs887829 and rs8175347 polymorphisms. Analysis of the joint effects of genotype and markers of estrogen exposure found the lowest risk of endometrial cancer among those with the homozygous variant genotype of the rs2070959 polymorphism and who were postmenopausal, had low body mass index, and had low soy food intake, although a test for multiplicative interaction was not significant. Taken together, these data suggest that the G/G genotype (rs2070959) in the UGT1A1 gene may decrease the risk of endometrial cancer and that this effect is most evident among women with low levels of endogenous estrogen exposure or with low soy food intake. 18349273 0 6 UGT1A1 Gene 54658 18349273 81 99 endometrial cancer Disease D016889 18349273 62 80 endometrial cancer Disease D016889 18349273 127 133 UGT1A1 Gene 54658 18349273 188 206 endometrial cancer Disease D016889 18349273 289 307 endometrial cancer Disease D016889 18349273 397 403 UGT1A1 Gene 54658 18349273 857 875 endometrial cancer Disease D016889 18349273 965 983 endometrial cancer Disease D016889 18349273 1115 1132 estrogen exposure Environment 54658-D016889 18349273 1158 1176 endometrial cancer Disease D016889 18349273 1483 1489 UGT1A1 Gene 54658 18349273 1520 1538 endometrial cancer Disease D016889 18349273 1593 1635 low levels of endogenous estrogen exposure Environment 54658-D016889 18349273 1644 1663 low soy food intake Environment 54658-D016889 19124504|t|Two estrogen-related variants in CYP19A1 and endometrial cancer risk: a pooled analysis in the Epidemiology of Endometrial Cancer Consortium. 19124504|t|Common variants in CYP19A1 (the A alleles of rs749292 and rs727479) have been associated with a 10% to 20% increase in circulating estrogen levels in postmenopausal women. We hypothesized that the presence of one or both A alleles in these single nucleotide polymorphisms (SNP) is associated with increased endometrial cancer risk. We tested this hypothesis in a large pooled analysis of 4,998 endometrial cancer cases and 8,285 controls from 10 studies in the Epidemiology of Endometrial Cancer Consortium. The majority of women (>66%) were whites, with smaller proportions of other races and ethnic groups (blacks, Asians, and Latinas) also included in this pooled analysis. Unconditional logistic regression was used to model the association between SNPs/haplotypes and endometrial cancer risk. Carrying the A allele of either of these SNPs was associated with an increased risk of endometrial cancer, with pooled odds ratios per allele of 1.14, 95% confidence interval of 1.09-1.21, and P = 7.1 x 10(-7) for rs749292, and odds ratio per allele of 1.08, 95% confidence interval of 1.02-1.14, and P = 0.009 for rs727479. For rs749292, these associations were generally stronger among women age >or=55 years. For both SNPs, risk increased with increasing body mass index, and for rs727479, this pattern seemed stronger among women age >or=55 years (P interaction = 0.007). The combination of A alleles in the two SNPs, either by direct count or by haplotype analysis, did not increase risk above that observed for the individual SNPs. Our study provides evidence that CYP19A1 genetic variation influences susceptibility to endometrial cancer, particularly among older and obese women. 19124504 33 40 CYP19A1 Gene 1588 19124504 45 63 endometrial cancer Disease D016889 19124504 111 129 Endometrial Cancer Disease D016889 19124504 19 26 CYP19A1 Gene 1588 19124504 307 325 endometrial cancer Disease D016889 19124504 394 412 endometrial cancer Disease D016889 19124504 477 495 Endometrial Cancer Disease D016889 19124504 773 791 endometrial cancer Disease D016889 19124504 885 903 endometrial cancer Disease D016889 19124504 1186 1208 women age >or=55 years Environment 1588-D016889 19124504 1245 1271 increasing body mass index Environment 1588-D016889 19124504 1326 1348 women age >or=55 years Environment 1588-D016889 19124504 1569 1576 CYP19A1 Gene 1588 19124504 1624 1642 endometrial cancer Disease D016889 19124504 1663 1684 older and obese women Environment 1588-D016889 19124504 1673 1678 obese Disease D009765 20395011|t|The CYP1B1 Leu432Val polymorphism contributes to lung cancer risk: evidence from 6501 subjects. 20395011|t|The polymorphism of cytochrome P4501B1 (CYP1B1) codon 432 (rs1056836, CYP1B1*3, or Leu432Val) is thought to have a significant effect on lung cancer risk, but the results are inconsistent. In this meta-analysis, we assessed 9 published studies involving 6501 subjects that investigated the association between the CYP1B1 codon 432 polymorphism and risk of lung cancer. Overall, the CYP1B1 Leu/Val and Val/Val-variant genotypes were associated with a significantly increased risk of lung cancer in different genetic models (heterozygote comparison: OR=1.22; 95% CI=1.02-1.45, P(heterogeneity)=0.068; homozygote comparison: OR=1.41; 95% CI=1.08-1.85, P(heterogeneity)=0.071; dominant model comparison: OR=1.26; 95% CI=1.04-1.51, P(heterogeneity)=0.019; and recessive model comparison: OR=1.17; 95% CI=1.02-1.34, P(heterogeneity)=0.429). In the stratified analysis by ethnicity, significantly increased risks were found among Caucasians for Leu/Val vs Leu/Leu (OR=1.30; 95% CI=1.03-1.64; P(heterogeneity)=0.092), and dominant model (OR=1.35; 95% CI=1.03-1.77; P(heterogeneity)=0.015). However, no significant associations were found in both Europeans and African-Americans for all genetic models. In the subgroup analyses by smoking status, a significantly increased risk of lung cancer was found among smokers (dominant model: OR=1.46; 95% CI=1.08-1.83; P(heterogeneity)=0.175). However, we did not find any statistically significant association by subgroup analyses of pathological type. This meta-analysis suggests that the CYP1B1 Val allele is a low-penetrant risk factor for developing lung cancer. 20395011 4 10 CYP1B1 Gene 1545 20395011 49 60 lung cancer Disease D008175 20395011 20 38 cytochrome P4501B1 Gene 1545 20395011 40 46 CYP1B1 Gene 1545 20395011 70 76 CYP1B1 Gene 1545 20395011 137 148 lung cancer Disease D008175 20395011 314 320 CYP1B1 Gene 1545 20395011 356 367 lung cancer Disease D008175 20395011 382 388 CYP1B1 Gene 1545 20395011 482 493 lung cancer Disease D008175 20395011 923 933 Caucasians Environment 1545-D008175 20395011 1272 1283 lung cancer Disease D008175 20395011 1300 1307 smokers Environment 1545-D008175 20395011 1524 1530 CYP1B1 Gene 1545 20395011 1588 1599 lung cancer Disease D008175 19960261|t|Glutathione S-transferase T1 (GSTT1) gene polymorphism and gastric cancer susceptibility: a meta-analysis of epidemiologic studies. 19960261|t|PURPOSE: Studies investigating the association between genetic polymorphism of glutathione S-transferase T1 (GSTT1) and gastric cancer risk have reported conflicting results. Therefore, we conducted this meta-analysis to provide more precise evidence. METHODS: We searched the databases Medline, PubMed, Embase, and China National Knowledge Infrastructure up to July 30, 2009. Thirty-six studies with 4,357 gastric cancer cases and 9,796 controls were selected. Odds ratio (OR) and 95% confidence intervals (CI) were calculated based on fixed- and random-effects models. RESULTS: The combined results based on all studies showed there was a significant link between GSTT1 null genotype and gastric cancer risk (OR = 1.14, 95%CI = 1.01-1.28). In subgroup analysis stratified on the basis of ethnic group, we also observed positive association between GSTT1 polymorphism and gastric cancer risk among Caucasians (non-Europeans + non-Americans), but not among East Asians. When stratifying by control source, the overall ORs for population- and hospital-based studies were 1.09 (95%CI = 0.94-1.28) and 1.17 (95%CI = 1.03-1.34), respectively. Subjects with both GSTM1 and GSTT1 negative genotypes had increased gastric cancer risk compared with those who had nonnull genotypes of both GST genes. Subgroup analyses for Helicobacter pylori infection and smoking habit did not reveal any significant association between GSTT1 polymorphism and gastric cancer development. CONCLUSIONS: This meta-analysis suggests that GSTT1 gene polymorphism may be not associated with increased gastric cancer risk among Europeans, Americans, and East Asians. More large-scale studies based on the same racial group are needed. 19960261 0 28 Glutathione S-transferase T1 Gene 2952 19960261 30 35 GSTT1 Gene 2952 19960261 59 73 gastric cancer Disease D013274 19960261 79 107 glutathione S-transferase T1 Gene 2952 19960261 109 114 GSTT1 Gene 2952 19960261 120 134 gastric cancer Disease D013274 19960261 407 421 gastric cancer Disease D013274 19960261 666 671 GSTT1 Gene 2952 19960261 690 704 gastric cancer Disease D013274 19960261 850 855 GSTT1 Gene 2952 19960261 873 887 gastric cancer Disease D013274 19960261 899 909 Caucasians Environment 2952-D013274 19960261 911 924 non-Europeans Environment 2952-D013274 19960261 927 940 non-Americans Environment 2952-D013274 19960261 1158 1163 GSTM1 Gene 2944 19960261 1168 1173 GSTT1 Gene 2952 19960261 1207 1221 gastric cancer Disease D013274 19960261 1334 1343 infection Disease D007239 19960261 1413 1418 GSTT1 Gene 2952 19960261 1436 1450 gastric cancer Disease D013274 19960261 1510 1515 GSTT1 Gene 2952 19960261 1571 1585 gastric cancer Disease D013274 18501970|t|The interaction of DRD2 and violent victimization on depression: an analysis by gender and race. 18501970|t|BACKGROUND: Recent research has shown that a polymorphism in the dopamine D2 receptor gene (DRD2) moderates the association between stressful life events and depression. The present study builds off this literature and examines whether DRD2 moderates the effect of violent victimization on depression. Furthermore, the current analyses investigate whether the effects of DRD2 and violent victimization vary by gender and by race for females. METHODS: Respondents from waves II and III of the National Longitudinal Study of Adolescent Health (Add Health) completed questionnaires regarding their depressive symptoms and violent victimization experiences (n = 2380). RESULTS: Multivariate regression results reveal that violent victimization has a strong independent effect on depressive symptoms for Caucasian females. In contrast, violent victimization is only associated with higher levels of depressive symptoms among African American females when they carry at least one A1 allele of DRD2. Results also show that DRD2 has a significant independent effect on depressive symptoms for males and African American females. CONCLUSIONS: The results suggest that African American females who carry the A1 allele of DRD2 may be more vulnerable to the negative effects of violent victimization than African American females who do not carry at least one copy of the A1 allele. LIMITATIONS: The current study's findings may not generalize to clinical populations, adults, and individuals residing in other countries. In addition, the effects of DRD2 may reflect other polymorphisms that are in linkage with DRD2. 18501970 19 23 DRD2 Gene 1813 18501970 28 49 violent victimization Environment 1813-D003866 18501970 53 63 depression Disease D003866 18501970 65 85 dopamine D2 receptor Gene 1813 18501970 92 96 DRD2 Gene 1813 18501970 132 153 stressful life events Environment 1813-D003866 18501970 158 168 depression Disease D003866 18501970 236 240 DRD2 Gene 1813 18501970 290 300 depression Disease D003866 18501970 371 375 DRD2 Gene 1813 18501970 595 614 depressive symptoms Disease D003866 18501970 775 794 depressive symptoms Disease D003866 18501970 831 852 violent victimization Disease 1 18501970 831 852 violent victimization Environment 1813-D003866 18501970 894 913 depressive symptoms Disease D003866 18501970 987 991 DRD2 Gene 1813 18501970 1016 1020 DRD2 Gene 1813 18501970 1061 1080 depressive symptoms Disease D003866 18501970 1211 1215 DRD2 Gene 1813 18501970 1266 1287 violent victimization Environment 1813-D003866 18501970 1538 1542 DRD2 Gene 1813 18501970 1600 1604 DRD2 Gene 1813 17854076|t|A variant of the Cockayne syndrome B gene ERCC6 confers risk of lung cancer. 17854076|t|Cockayne syndrome B protein (ERCC6) plays an essential role in DNA repair. However, the Cockayne syndrome caused by the ERCC6 defect has not been linked to cancer predisposition; likely due to the fact that cells with severe disruption of the ERCC6 function are sensitive to lesion-induced apoptosis, thus reducing the chance of tumorigenesis. The biological function and cancer susceptibility of a common variant rs3793784:C>G (c.-6530C>G) in the ERCC6 was examined. We show that the c.-6530C allele has lower binding affinity of Sp1 by EMSA and displays a lower transcriptional activity in vitro and in vivo. We then examined the contribution of this polymorphism to the risk of lung cancer in a case-control study with 1,000 cases and 1,000 controls. The case-control analysis revealed a 1.76-fold (P= x 10(-9)) excess risk of developing lung cancer for the c.-6530CC carriers compared with noncarriers. The c.-6530CC interacts with smoking to intensify lung cancer risk, with the odds ratio (OR)=9 for developing lung cancer among heavy smokers. Our data constituted strong evidence that ERCC6 rs3793784:C>G alters its transcriptional activity and may confer personalized susceptibility to lung cancer. 17854076 17 34 Cockayne syndrome Disease D003057 17854076 42 47 ERCC6 Gene 2074 17854076 64 75 lung cancer Disease D008175 17854076 0 17 Cockayne syndrome Disease D003057 17854076 29 34 ERCC6 Gene 2074 17854076 88 105 Cockayne syndrome Disease D003057 17854076 120 125 ERCC6 Gene 2074 17854076 156 162 cancer Disease D009369 17854076 243 248 ERCC6 Gene 2074 17854076 329 342 tumorigenesis Disease D063646 17854076 372 378 cancer Disease D009369 17854076 448 453 ERCC6 Gene 2074 17854076 531 534 Sp1 Gene 6667 17854076 681 692 lung cancer Disease D008175 17854076 841 852 lung cancer Disease D008175 17854076 936 943 smoking Environment 2074-D008175 17854076 957 968 lung cancer Disease D008175 17854076 1017 1028 lung cancer Disease D008175 17854076 1035 1048 heavy smokers Environment 2074-D008175 17854076 1092 1097 ERCC6 Gene 2074 17854076 1194 1205 lung cancer Disease D008175 16344274|t|ADH3 genotype, alcohol intake and breast cancer risk. 16344274|t|Moderate alcohol consumption of approximately 1-2 drinks per day has been associated with a 30-50% increase in breast cancer risk. Individuals differ in their ability to metabolize alcohol through genetic differences in alcohol dehydrogenase (ADH), the enzyme that catalyzes the oxidation of approximately 80% of ethanol to acetaldehyde, a known carcinogen. Individuals differ in their ADH genotype, and one locus in particular (ADH3) is polymorphic in Caucasian populations. Using data from the Long Island Breast Cancer Study Project, we examined whether fast metabolizers of alcohol, as measured by the ADH3(1-1) genotype, have a higher risk of breast cancer from alcohol intake compared with those individuals who are slow metabolizers, but consume similar amounts of alcohol. We combined genotyping information with questionnaire data on 1047 breast cancer cases and 1101 controls and used unconditional logistic regression methods to estimate multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) between alcohol intake and breast cancer risk. Among individuals homozygous for the fast metabolizing allele (ADH(3)1-1), a lifetime alcohol consumption of 15-30 g/day (approximately 1-2 drinks per day) increased breast cancer risk by 2-fold (OR=2.0, 95% CI=1.1-3.5). In contrast, the increase in risk from a lifetime alcohol consumption of 15-30 g/day was less pronounced in the intermediate and slow metabolizing groups, respectively: ADH3(1-2) (OR=1.5, 95% CI 0.9-2.4) and ADH(3)2-2 (OR=1.3, 95% CI 0.5-3.5). Fast metabolizers who drank 15-30 g/day of alcohol had 2.3 times (95% CI 1.3-4.0) greater risk of breast cancer than non-drinkers who were intermediate or slow metabolizers. This association for fast metabolizers who drank 15-30 g/day was particularly pronounced among premenopausal women (premenopausal women OR=2.9, 95 % CI=1.2-7.1; postmenopausal women OR=1.8, 95% CI=0.9-3.8). These population-based data support the hypothesis that fast metabolizers of alcohol have a higher risk of breast cancer risk, from alcohol intake than slow metabolizers. 16344274 0 4 ADH3 Gene 126 16344274 34 47 breast cancer Disease D001943 16344274 111 124 breast cancer Disease D001943 16344274 429 433 ADH3 Gene 126 16344274 606 610 ADH3 Gene 126 16344274 648 661 breast cancer Disease D001943 16344274 848 861 breast cancer Disease D001943 16344274 1051 1064 breast cancer Disease D001943 16344274 1146 1226 a lifetime alcohol consumption of 15-30 g/day (approximately 1-2 drinks per day) Environment 126-D001943 16344274 1237 1250 breast cancer Disease D001943 16344274 1331 1376 a lifetime alcohol consumption of 15-30 g/day Environment 126-D001943 16344274 1461 1465 ADH3 Gene 126 16344274 1554 1586 who drank 15-30 g/day of alcohol Environment 126-D001943 16344274 1634 1647 breast cancer Disease D001943 16344274 1749 1770 who drank 15-30 g/day Environment 126-D001943 16344274 1994 2001 alcohol Environment 126-D001943 16344274 2024 2037 breast cancer Disease D001943 16344274 2049 2063 alcohol intake Environment 126-D001943 19184334|t|Transcription factor AP-2 beta genotype and psychosocial adversity in relation to adolescent depressive symptomatology. 19184334|t|The aim of this study was to investigate possible interactions between the gene coding for activating protein-2 beta (AP-2 beta) and psychosocial factors to predict depressive symptoms in adolescents. Two-hundred 16- and 19-year-old adolescents from the county of Vastmanland, Sweden, were asked to complete a questionnaire, interviewed about psychosocial risk factors, and genotyped with regard to the transcription factor AP-2 beta intron 2 polymorphism. AP-2 beta genotype interacted significantly both with type of housing and parental separation to predict depressive symptoms. Individuals who were homozygous for the short AP-2 beta allele displayed higher depression scores when psychosocial adversity was taken into account. Amongst carriers of one or two copies of the long allele, there was no difference in depressive symptoms despite differences in psychosocial environments. 19184334 21 30 AP-2 beta Gene 7021 19184334 44 66 psychosocial adversity Environment 7021-D003866 19184334 93 103 depressive Disease D003866 19184334 118 127 AP-2 beta Gene 7021 19184334 165 184 depressive symptoms Disease D003866 19184334 424 433 AP-2 beta Gene 7021 19184334 457 466 AP-2 beta Gene 7021 19184334 501 550 both with type of housing and parental separation Environment 7021-D003866 19184334 562 581 depressive symptoms Disease D003866 19184334 629 638 AP-2 beta Gene 7021 19184334 663 673 depression Disease D003866 19184334 686 708 psychosocial adversity Environment 7021-D003866 19184334 818 837 depressive symptoms Disease D003866 21614524|t|Association of ERCC2/XPD polymorphisms and interaction with tobacco smoking in lung cancer susceptibility: a systemic review and meta-analysis. 21614524|t|The association of the two ERCC polymorphisms, Asp312Asn and Lys751Gln, with lung cancer risk remains controversial and inconclusive. To better evaluate the potential role of the two polymorphisms and interaction with tobacco smoking in lung cancer susceptibility presented in diverse populations, we have conducted a meta-analysis based on 26 studies from 24 publications which included analyses of Asp312Asn (7121 cases, 8962 controls) and Lys751Gln (8396 cases, 10510 controls) polymorphisms. Overall, significantly elevated lung cancer risk was associated with ERCC2 312Asn allele(homozygous model: OR=1.20[1.05-1.36], P=0.006; recessive model: OR=1.20[1.06-1.35], P=0.004) and 751Gln allele(homozygous model: OR=1.31[1.17-1.46], P<0.00001; heterozygous model: OR=1.11[1.04-1.19], P=0.003; recessive model: OR=1.23[1.11-1.37], P<0.0001; dominant model: OR=1.15[1.08-1.23], P<0.0001). In ethnic subgroup analyses, significantly increased risk was associated with ERCC2 312Asn allele for both Caucasians and Asians, and 751Gln allele for both Caucasians and Latino-Americans. When stratified by smoking status, significantly elevated risk of both polymorphisms for never-smokers was detected (dominant model, OR=1.46[1.09-1.95] and 1.57[1.19-2.08], P=0.01 and 0.002, respectively). In conclusion, this meta-analysis suggests that the two ERCC2 polymorphisms may contribute to lung cancer susceptibility serving as low-penetrance risk factors. Extremely large-scale evidence would be necessary to confirm the effects on ethnically specific populations and gene-environment interactions. 21614524 15 20 ERCC2 Gene 2068 21614524 21 24 XPD Gene 2068 21614524 79 90 lung cancer Disease D008175 21614524 77 88 lung cancer Disease D008175 21614524 237 248 lung cancer Disease D008175 21614524 528 539 lung cancer Disease D008175 21614524 565 570 ERCC2 Gene 2068 21614524 966 971 ERCC2 Gene 2068 21614524 990 1000 Caucasians Environment 2068-D010051 21614524 1005 1011 Asians Environment 2068-D010051 21614524 1040 1050 Caucasians Environment 2068-D010051 21614524 1055 1071 Latino-Americans Environment 2068-D010051 21614524 1162 1175 never-smokers Environment 2068-D010051 21614524 1335 1340 ERCC2 Gene 2068 21614524 1373 1384 lung cancer Disease D008175 21614524 1516 1547 ethnically specific populations Environment 2068-D010051 11207350|t|Genetic variation in alcohol dehydrogenase and the beneficial effect of moderate alcohol consumption on myocardial infarction. 11207350|t|BACKGROUND: A polymorphism in the gene for alcohol dehydrogenase type 3 (ADH3) alters the rate of alcohol metabolism. We investigated the relation among the ADH3 polymorphism, the level of alcohol consumption, and the risk of myocardial infarction in a nested case-control study based on data from the prospective Physicians' Health Study. METHODS: We identified 396 patients with eligible newly diagnosed cases of myocardial infarction among men in the Physicians' Health Study. Of these patients, 374 were matched with 2 randomly selected control subjects each and the remaining 22 with 1 control each (total, 770 controls). The ADH3 genotype (gamma1gamma1, gamma1gamma2, or gamma2gamma2) was determined in all subjects. We examined the relations among the level of alcohol intake, the ADH3 genotype, and plasma high-density lipoprotein (HDL) levels in this study population and in a similar cohort of women. RESULTS: As compared with homozygosity for the allele associated with a fast rate of ethanol oxidation (gamma1), homozygosity for the allele associated with a slow rate of ethanol oxidation (gamma2) was associated with a reduced risk of myocardial infarction (relative risk, 0.65; 95 percent confidence interval, 0.43 to 0.99). Moderate alcohol consumption was associated with a decreased risk of myocardial infarction in all three genotype groups (gamma1gamma1, gamma1gamma2, and gamma2gamma2); however, the ADH3 genotype significantly modified this association (P=0.01 for the interaction). Among men who were homozygous for the gamma1 allele, those who consumed at least one drink per day had a relative risk of myocardial infarction of 0.62 (95 percent confidence interval, 0.34 to 1.13), as compared with the risk among men who consumed less than one drink per week. Men who consumed at least one drink per day and were homozygous for the gamma2 allele had the greatest reduction in risk (relative risk, 0.14; 95 percent confidence interval, 0.04 to 0.45). Such men also had the highest plasma HDL levels (P for interaction = 0.05). We confirmed the interaction among the ADH3 genotype, the level of alcohol consumption, and the HDL level in an independent study of postmenopausal women (P=0.02). CONCLUSIONS: Moderate drinkers who are homozygous for the slow-oxidizing ADH3 allele have higher HDL levels and a substantially decreased risk of myocardial infarction. 11207350 104 125 myocardial infarction Disease D009203 11207350 43 71 alcohol dehydrogenase type 3 Gene 126 11207350 73 77 ADH3 Gene 126 11207350 157 161 ADH3 Gene 126 11207350 226 247 myocardial infarction Disease D009203 11207350 415 436 myocardial infarction Disease D009203 11207350 631 635 ADH3 Gene 126 11207350 788 792 ADH3 Gene 126 11207350 1148 1169 myocardial infarction Disease D009203 11207350 1239 1267 Moderate alcohol consumption Environment 126-D009203 11207350 1308 1329 myocardial infarction Disease D009203 11207350 1420 1424 ADH3 Gene 126 11207350 1563 1602 who consumed at least one drink per day Environment 126-D009203 11207350 1626 1647 myocardial infarction Disease D009203 11207350 1787 1826 who consumed at least one drink per day Environment 126-D009203 11207350 2088 2092 ADH3 Gene 126 11207350 2103 2135 the level of alcohol consumption Environment 126-D009203 11207350 2226 2243 Moderate drinkers Environment 126-D009203 11207350 2286 2290 ADH3 Gene 126 11207350 2359 2380 myocardial infarction Disease D009203 18771913|t|Associations between XPC polymorphisms and risk of cancers: A meta-analysis. 18771913|t|Several polymorphisms (Lys(939)Gln, PAT+/- and Ala(499)Val) in the DNA nuclear excision repair gene xeroderma pigmentosum complementation group C (XPC) are thought to have significant effects on cancer risk. In this meta-analysis, we assessed reported studies of associations between three XPC polymorphisms and risk of cancers from 16 studies with 6797 cases and 9018 controls for Lys(939)Gln, from 11 studies with 5581 cases and 6351 controls for Ala(499)Val and from 16 studies with 4514 cases and 5538 controls for PAT+/-. We found an increased overall cancer risk for variant homozygotes of Lys(939)Gln (OR=1.16, 95% CI, 1.05-1.28) and Ala(499)Val (OR=1.24, 95% CI, 1.08-1.42) compared with their corresponding wild-type homozygotes. When stratified by cancer type, the variant (939)Gln homozygous genotype was a risk factor for lung cancer (OR=1.28, 95% CI, 1.07-1.53), whereas the (499)Val variant homozygous genotype was a risk factor for bladder cancer (OR=1.33, 95% CI, 1.06-1.68) compared with their corresponding wild-type homozygous genotypes. For the XPC-PAT polymorphism, we found a decreased cancer risk associated with the PAT+/- genotype only in Asians compared with the PAT-/- genotype. Five studies were pooled for stratification analysis to explore the gene-smoking interaction. There was a joint effect of PAT +/+ and smoking in cancer risk. These analyses suggest that XPC Lys(939)Gln, PAT+/- and Ala(499)Val likely contribute to susceptibility to cancers. However, single larger studies with subjects of the same ethnic background and tissue-specific biochemical and biological characterisation are warranted to validate these findings. 18771913 21 24 XPC Gene 7508 18771913 51 58 cancers Disease D009369 18771913 100 145 xeroderma pigmentosum complementation group C Gene 7508 18771913 100 109 xeroderma Disease D007057 18771913 147 150 XPC Gene 7508 18771913 195 201 cancer Disease D009369 18771913 290 293 XPC Gene 7508 18771913 320 327 cancers Disease D009369 18771913 557 563 cancer Disease D009369 18771913 758 764 cancer Disease D009369 18771913 834 845 lung cancer Disease D008175 18771913 834 845 lung cancer Environment 7508-D009369 18771913 947 961 bladder cancer Disease D001749 18771913 947 961 bladder cancer Environment 7508-D009369 18771913 1065 1068 XPC Gene 7508 18771913 1108 1114 cancer Disease D009369 18771913 1164 1170 Asians Environment 7508-D009369 18771913 1340 1347 smoking Environment 7508-D009369 18771913 1351 1357 cancer Disease D009369 18771913 1392 1395 XPC Gene 7508 18771913 1471 1478 cancers Disease D009369 17416766|t|IL6, aspirin, nonsteroidal anti-inflammatory drugs, and breast cancer risk in women living in the southwestern United States. 17416766|t|Interleukin-6 is a cytokine thought to be involved in inflammation, insulin, and estrogen-related pathways. We evaluate genetic variation in the IL6 gene with risk of breast cancer. We also evaluate breast cancer associations with aspirin and nonsteroidal anti-inflammatory drugs. A breast cancer case-control study (n = 1,527 non-Hispanic white cases, 1,601 non-Hispanic white controls, 798 Hispanic/Native American cases, and 924 Hispanic/Native American controls) was conducted among women living in the southwestern United States (4-Corner's Breast Cancer Study). Five IL6 single nucleotide polymorphisms (SNP) and IL6 haplotypes based on these SNPs were evaluated. Allele frequencies were significantly different between non-Hispanic white and Hispanic/Native American women. Among postmenopausal women not recently exposed to hormones, the AG/GG genotypes of rs1800797 (-596A>G) and the GC/CC genotypes of rs1800795 (-174G>C) significantly reduced risk of breast cancer among non-Hispanic white women [odds ratio (OR), 0.69; 95% confidence interval (95% CI), 0.48-1.00 and OR, 0.68; 95% CI, 0.47-0.99, respectively] and Hispanic/Native American women (OR, 0.48; 95% CI, 0.28-0.83 and OR, 0.44; 95% CI, 0.26-0.99, respectively). Haplotypes of the five IL6 SNPs further defined these associations. Recent aspirin use significantly decreased risk of breast cancer among postmenopausal Hispanic/Native American women not recently exposed to hormones (OR, 0.56; 95% CI, 0.33-0.96). Among non-Hispanic white, the inverse association with aspirin was not statistically significant. IL6 genotype and haplotype significantly modified the association between aspirin and breast cancer, with the greatest effect modification being among women not recently exposed to hormones [P interaction = 0.06 (for non-Hispanic white) and 0.04 (for Hispanic/Native American) and SNP rs1800796 or -572G>C]. These data suggest that IL6 is associated with breast cancer risk and modifies the association between estrogen and aspirin and breast cancer risk. 17416766 0 3 IL6 Gene 3569 17416766 56 69 breast cancer Disease D001943 17416766 0 13 Interleukin-6 Gene 3569 17416766 54 66 inflammation Disease D007249 17416766 145 148 IL6 Gene 3569 17416766 167 180 breast cancer Disease D001943 17416766 199 212 breast cancer Disease D001943 17416766 283 296 breast cancer Disease D001943 17416766 546 559 Breast Cancer Disease D001943 17416766 573 576 IL6 Gene 3569 17416766 619 622 IL6 Gene 3569 17416766 787 840 postmenopausal women not recently exposed to hormones Environment 3569-D001943 17416766 962 975 breast cancer Disease D001943 17416766 1257 1260 IL6 Gene 3569 17416766 1302 1320 Recent aspirin use Environment 3569-D001943 17416766 1353 1366 breast cancer Disease D001943 17416766 1581 1584 IL6 Gene 3569 17416766 1655 1662 aspirin Environment 3569-D001943 17416766 1667 1680 breast cancer Disease D001943 17416766 1732 1770 women not recently exposed to hormones Environment 3569-D001943 17416766 1913 1916 IL6 Gene 3569 17416766 1936 1949 breast cancer Disease D001943 17416766 1992 2000 estrogen Environment 3569-D001943 17416766 2005 2012 aspirin Environment 3569-D001943 17416766 2017 2030 breast cancer Disease D001943 16912209|t|Sequence variants in cell cycle control pathway, X-ray exposure, and lung cancer risk: a multicenter case-control study in Central Europe. 16912209|t|Exposure to ionizing radiation (IR) results in various types of DNA damage and is a suspected cause of lung cancer. An essential cellular machinery against DNA damage is cell cycle control, which is regulated by several genes, including TP53, CCND1, and CDKN2A. Therefore, we hypothesized that the genetic variants in these three genes influence the predisposition of lung cancer (i.e., CCND1 G870A, CDKN2A Ala(148)Thr, TP53 Arg(72)Pro, and 16-bp repeat in intron 3) and that the effect of X-ray on lung cancer risk can be modified by the presence of these genetic variations. The study was conducted in 15 centers in 6 countries of Central Europe between 1998 and 2002. A total of 2,238 cases and 2,289 controls were recruited and provided DNA samples. Cases with positive family history were analyzed separately. The joint effect of X-ray and previous risk genotypes was assessed, and modification by sequence variants on X-ray dose-response relationship with lung cancer risk was evaluated. We found an overall effect of TP53 intron 3 16-bp repeats [odds ratio (OR), 1.99; 95% confidence interval (95% CI), 1.27-3.13], which was stronger among cases with family history of lung cancer (OR, 2.98; 95% CI, 1.29-6.87). In addition, our results suggested an interaction that was greater than multiplicativity between TP53 intron 3 16-bp repeats and multiple X-ray exposures (interaction OR, 5.69; 95% CI, 1.33-24.3). We did not observe a main effect of CCND1 G870A polymorphism; however, the dose-response relationship between lung cancer risk and X-ray exposures was modified by CCND1 genotype with no risk from X-ray exposures among subjects who carried G/G genotype, intermediate risk [trend OR for X-ray, 1.16; 95% CI, 1.05-1.27) among subjects with G/A genotype, and highest risk [trend OR for X-ray, 1.29; 95% CI, 1.12-1.49) among subjects with A/A genotype. Sequence variants in cell cycle control pathway may increase the risk of lung cancer and modify the risk conferred by multiple X-ray exposures. However, a definite conclusion can only be drawn on replication by different studies among individuals who are highly exposed to IR. 16912209 69 80 lung cancer Disease D008175 16912209 103 114 lung cancer Disease D008175 16912209 237 241 TP53 Gene 7157 16912209 243 248 CCND1 Gene 595 16912209 254 260 CDKN2A Gene 1029 16912209 368 379 lung cancer Disease D008175 16912209 387 392 CCND1 Gene 595 16912209 400 406 CDKN2A Gene 1029 16912209 420 424 TP53 Gene 7157 16912209 499 510 lung cancer Disease D008175 16912209 962 973 lung cancer Disease D008175 16912209 1024 1028 TP53 Gene 7157 16912209 1158 1187 family history of lung cancer Environment 7157-D008175 16912209 1176 1187 lung cancer Disease D008175 16912209 1316 1320 TP53 Gene 7157 16912209 1348 1372 multiple X-ray exposures Environment 7157-D008175 16912209 1452 1457 CCND1 Gene 595 16912209 1526 1537 lung cancer Disease D008175 16912209 1547 1562 X-ray exposures Environment 595-D008175 16912209 1579 1584 CCND1 Gene 595 16912209 1937 1948 lung cancer Disease D008175 16912209 1982 2006 multiple X-ray exposures Environment 595-D008175 16912209 1982 2006 multiple X-ray exposures Environment 7157-D008175 20679621|t|Fatty acid synthase polymorphisms, tumor expression, body mass index, prostate cancer risk, and survival. 20679621|t|PURPOSE: Fatty acid synthase (FASN) regulates de novo lipogenesis, body weight, and tumor growth. We examined whether common germline single nucleotide polymorphisms (SNPs) in the FASN gene affect prostate cancer (PCa) risk or PCa-specific mortality and whether these effects vary by body mass index (BMI). METHODS: In a prospective nested case-control study of 1,331 white patients with PCa and 1,267 age-matched controls, we examined associations of five common SNPs within FASN (and 5 kb upstream/downstream, R(2) > 0.8) with PCa incidence and, among patients, PCa-specific death and tested for an interaction with BMI. Survival analyses were repeated for tumor FASN expression (n = 909). RESULTS: Four of the five SNPs were associated with lethal PCa. SNP rs1127678 was significantly related to higher BMI and interacted with BMI for both PCa risk (P(interaction) = .004) and PCa mortality (P(interaction) = .056). Among overweight men (BMI > or = 25 kg/m(2)), but not leaner men, the homozygous variant allele carried a relative risk of advanced PCa of 2.49 (95% CI, 1.00 to 6.23) compared with lean men with the wild type. Overweight patients carrying the variant allele had a 2.04 (95% CI, 1.31 to 3.17) times higher risk of PCa mortality. Similarly, overweight patients with elevated tumor FASN expression had a 2.73 (95% CI, 1.05 to 7.08) times higher risk of lethal PCa (P(interaction) = .02). CONCLUSION: FASN germline polymorphisms were significantly associated with risk of lethal PCa. Significant interactions of BMI with FASN polymorphisms and FASN tumor expression suggest FASN as a potential link between obesity and poor PCa outcome and raise the possibility that FASN inhibition could reduce PCa-specific mortality, particularly in overweight men. 20679621 0 19 Fatty acid synthase Gene 2194 20679621 35 40 tumor Disease D009369 20679621 70 85 prostate cancer Disease D011471 20679621 9 28 Fatty acid synthase Gene 2194 20679621 30 34 FASN Gene 2194 20679621 67 78 body weight Disease D001835 20679621 84 89 tumor Disease D009369 20679621 180 184 FASN Gene 2194 20679621 197 212 prostate cancer Disease D011471 20679621 214 217 PCa Disease D011471 20679621 227 230 PCa Disease D011471 20679621 388 391 PCa Disease D011471 20679621 476 480 FASN Gene 2194 20679621 529 532 PCa Disease D011471 20679621 564 567 PCa Disease D011471 20679621 659 664 tumor Disease D009369 20679621 665 669 FASN Gene 2194 20679621 751 754 PCa Disease D011471 20679621 799 809 higher BMI Environment 2194-D011471 20679621 830 833 BMI Environment 2194-D011471 20679621 843 846 PCa Disease D011471 20679621 880 883 PCa Disease D011471 20679621 925 935 overweight Disease D050177 20679621 925 963 overweight men (BMI > or = 25 kg/m(2)) Environment 2194-D011471 20679621 1051 1054 PCa Disease D011471 20679621 1129 1139 Overweight Disease D050177 20679621 1129 1148 Overweight patients Environment 2194-D011471 20679621 1232 1235 PCa Disease D011471 20679621 1258 1268 overweight Disease D050177 20679621 1258 1277 overweight patients Environment 2194-D011471 20679621 1292 1297 tumor Disease D009369 20679621 1298 1302 FASN Gene 2194 20679621 1376 1379 PCa Disease D011471 20679621 1416 1420 FASN Gene 2194 20679621 1494 1497 PCa Disease D011471 20679621 1527 1530 BMI Environment 2194-D011471 20679621 1536 1540 FASN Gene 2194 20679621 1559 1563 FASN Gene 2194 20679621 1564 1569 tumor Disease D009369 20679621 1589 1593 FASN Gene 2194 20679621 1622 1629 obesity Disease D009765 20679621 1622 1629 obesity Environment 2194-D011471 20679621 1639 1642 PCa Disease D011471 20679621 1682 1686 FASN Gene 2194 20679621 1711 1714 PCa Disease D011471 20679621 1751 1761 overweight Disease D050177 20679621 1751 1765 overweight men Environment 2194-D011471 18789576|t|Meta-analyses of the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and risk of head and neck and lung cancer. 18789576|t|Authors report the results of four meta-analyses of studies that examined the association between methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and head and neck cancer (nine studies, 2076 cases and 4834 controls for C677T; four studies, 1439 cases and 3941 controls for A1298C), and lung cancer (ten studies, 5274 cases and 7435 controls for C677T; seven studies, 5098 cases and 6243 controls for A1298C). The summary odds ratio (OR) of head and neck cancer was 0.92 (95% CI: 0.76-1.11) for MTHFR 677 TT and 0.68 (95% CI: 0.37-1.26) for MTHFR 1298 CC. The OR of lung cancer was 1.22 [95% confidence interval (CI): 0.95-1.55] for MTHFR 677 TT and 1.07 (95% CI: 0.83-1.38) for MTHFR 1298 CC. Results from the meta-analysis of three studies on C677T stratified according to dietary folate intake showed an increased risk for individuals with low folate intake (OR = 1.37, 95% CI: 0.92-2.06 for head and neck and OR = 1.28, 95% CI: 0.97-1.68 for lung) versus high folate intake (OR = 0.85, 95% CI: 0.63-1.16 for head and neck, and OR = 0.94, 95% CI: 0.79-1.12 for lung). Despite the lack of formal statistical significance, these findings are consistent with the hypothesis that folate play a role in lung and head/neck carcinogenesis, and show the need to incorporate data on folate intake when interpreting results of MTHFR polymorphisms in relation to cancer risk. 18789576 21 56 methylenetetrahydrofolate reductase Gene 4524 18789576 118 129 lung cancer Disease D008175 18789576 98 133 methylenetetrahydrofolate reductase Gene 4524 18789576 135 140 MTHFR Gene 4524 18789576 177 197 head and neck cancer Disease D006258 18789576 313 324 lung cancer Disease D008175 18789576 467 487 head and neck cancer Disease D006258 18789576 521 526 MTHFR Gene 4524 18789576 567 572 MTHFR Gene 4524 18789576 592 603 lung cancer Disease D008175 18789576 659 664 MTHFR Gene 4524 18789576 705 710 MTHFR Gene 4524 18789576 869 886 low folate intake Environment 4524-D008175 18789576 869 886 low folate intake Environment 4524-D006258 18789576 985 1003 high folate intake Environment 4524-D008175 18789576 985 1003 high folate intake Environment 4524-D006258 18789576 1205 1211 folate Environment 4524-D008175 18789576 1205 1211 folate Environment 4524-D006258 18789576 1246 1260 carcinogenesis Disease D063646 18789576 1303 1316 folate intake Environment 4524-D008175 18789576 1303 1316 folate intake Environment 4524-D006258 18789576 1346 1351 MTHFR Gene 4524 18789576 1381 1387 cancer Disease D009369 16788379|t|Polymorphisms in O6-methylguanine DNA methyltransferase and breast cancer risk. 16788379|t|OBJECTIVE: Endogenous and exogenous estrogens influence breast cancer risk by interacting with estrogen receptor (ER). The O-methylguanine DNA methyltransferase (MGMT) gene has a dual role in repairing alkylation damage and in inhibiting ER-mediated cell proliferation. We assessed the two MGMT polymorphisms, Leu84Phe and Ile143Val, with breast cancer risk. We also evaluated the potential interactions between the two polymorphisms and estrogen-related risk factors and cigarette smoking on breast cancer risk. METHODS: We conducted a nested case-control study within the Nurses' Health Study (1311 cases, 1760 controls). RESULTS: Compared with the 84Leu/Leu genotype, the Phe/Phe genotype had a multivariate odds ratio (OR) of 1.68 (95% confidence interval (CI), 0.98-2.88). This positive association was magnified among postmenopausal women with body mass index>25 (OR, 3.01; 95% CI, 1.30-6.94), those in the highest tertile of pre-diagnostic plasma endogenous estradiol levels (Phe carriers versus non-carriers, OR, 2.42; 95% CI, 1.49-3.94), non-current postmenopausal hormone users (OR, 2.60; 95% CI, 1.19-5.64), and possibly estrogen receptor-positive cases (OR, 1.82; 95% CI, 0.99-3.35). We did not observe a main effect of the Ile143Val polymorphism or its interactions with these factors. No interaction was observed between either of the polymorphisms and cigarette smoking on breast cancer risk. CONCLUSIONS: These data suggest that the Leu84Phe polymorphism affect the capacity of MGMT to inhibit estrogen receptor-mediated cell proliferation and is associated with breast cancer risk. 16788379 17 55 O6-methylguanine DNA methyltransferase Gene 4255 16788379 60 73 breast cancer Disease D001943 16788379 56 69 breast cancer Disease D001943 16788379 95 112 estrogen receptor Gene 2099 16788379 114 116 ER Gene 2099 16788379 123 160 O-methylguanine DNA methyltransferase Gene 4255 16788379 162 166 MGMT Gene 4255 16788379 238 240 ER Gene 2099 16788379 290 294 MGMT Gene 4255 16788379 339 352 breast cancer Disease D001943 16788379 493 506 breast cancer Disease D001943 16788379 850 868 body mass index>25 Environment 4255-D001943 16788379 909 981 the highest tertile of pre-diagnostic plasma endogenous estradiol levels Environment 4255-D001943 16788379 1047 1087 noe-current postmenopausal hormone users Environment 4255-D001943 16788379 1132 1149 estrogen receptor Gene 2099 16788379 1132 1164 estrogen receptor-positive cases Environment 4255-D001943 16788379 1388 1401 breast cancer Disease D001943 16788379 1494 1498 MGMT Gene 4255 16788379 1510 1527 estrogen receptor Gene 2099 16788379 1579 1592 breast cancer Disease D001943 20308031|t|Functional polymorphisms to modulate luminal lipid exposure and risk of colorectal cancer. 20308031|t|PURPOSE: Fat absorption may play a crucial role in colorectal carcinogenesis by determining intra-colonic exposure to potentially carcinogenic lipid metabolites. METHODS: We conducted a population-based case-control study that included 1163 cases and 1501 controls to examine whether individuals who carry genetic variants associated with lower lipid absorption have a higher risk of colorectal cancer. Using Taqman assay, we determined FABP2 alanine (A)/threonine (T) polymorphism at codon 54 in exon-2 and APOE isoforms. Multivariable odds ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression models, assuming FABP2 A54 and APO non-E4 as high risk alleles. RESULTS: We found no associations with either of the polymorphisms. The OR associated with FABP2 A54 homozygotes compared with the others was 1.01 (95% CI; 0.86-1.45) and that for non-ApoE4 carriers compared with carries was 0.95 (95% CI; 0.80-1.13). However, there was a statistically significant negative interaction between total fat intake and FABP2 AA genotypes (p=0.025), indicating that the risk of colorectal cancer associated with this polymorphism is higher in the subjects with lower fat intake. CONCLUSIONS: These results suggest that these SNPs may not be useful in predicting colorectal cancer risk in populations with high fat intake. 20308031 72 89 colorectal cancer Disease D015179 20308031 51 76 colorectal carcinogenesis Disease 1 20308031 130 142 carcinogenic Disease D063646 20308031 384 401 colorectal cancer Disease D015179 20308031 437 442 FABP2 Gene 2169 20308031 508 512 APOE Gene 348 20308031 658 663 FABP2 Gene 2169 20308031 796 801 FABP2 Gene 2169 20308031 889 894 ApoE4 Gene 348 20308031 1053 1058 FABP2 Gene 2169 20308031 1111 1128 colorectal cancer Disease D015179 20308031 1194 1210 lower fat intake Environment 2169-D015179 20308031 1295 1312 colorectal cancer Disease D015179 20308031 1338 1353 high fat intake Environment 2169-D015179 22223435|t|EGFR mutations in non-small-cell lung cancer among smokers and non-smokers: a meta-analysis. 22223435|t|Mounting evidence has suggested somatic mutations in the EGFR gene are associated with better responsiveness to EGFR tyrosine kinase inhibitors (TKIs) in patients with non-small-cell lung cancer (NSCLC). Some, but not all, studies have reported that the mutations were more frequently observed in patients without a smoking history. To comprehensively address this issue, we performed a meta-analysis to evaluate the association between cigarette-smoking history and mutation of the EGFR gene in NSCLC. Twenty-six studies, involving 3,688 patients with NSCLC were included in the analysis. The pooled analysis shows that the incidence of EGFR mutations in NSCLC differs according to cigarette-smoking history. The odds ratio (OR) for the EGFR mutation in non-smokers relative to smokers was 4.829 (95% confidence interval [CI]: 3.598-6.482; P < 0.001). These data may assist clinicians in assessing the likelihood of EGFR mutations in patients with NSCLC when mutational analysis is not feasible. 22223435 0 4 EGFR Gene 1956 22223435 33 44 lung cancer Disease D008175 22223435 57 61 EGFR Gene 1956 22223435 112 116 EGFR Gene 1956 22223435 183 194 lung cancer Disease D008175 22223435 196 201 NSCLC Disease D002289 22223435 483 487 EGFR Gene 1956 22223435 496 501 NSCLC Disease D002289 22223435 553 558 NSCLC Disease D002289 22223435 638 642 EGFR Gene 1956 22223435 656 661 NSCLC Disease D002289 22223435 683 708 cigarette-smoking history Environment 1956-D002289 22223435 738 742 EGFR Gene 1956 22223435 755 766 non-smokers Environment 1956-D002289 22223435 917 921 EGFR Gene 1956 22223435 949 954 NSCLC Disease D002289 16837478|t|CYP2E1PstI/RsaI polymorphism and interaction with tobacco, alcohol and GSTs in gastric cancer susceptibility: A meta-analysis of the literature. 16837478|t|Studies investigating the association between cytochrome P450 2E1 (CYP2E1) 5'-flanking region (PstI/RsaI) polymorphism and gastric cancer risk report conflicting results. The rationale for this meta-analysis was to determine whether CYP2E1*2 (c2) variant allele of CYP2E1 increases gastric cancer risk, especially by interacting with smoking, alcohol and other metabolic gene polymorphisms. Two investigators independently searched the Medline and Embase databases. A qualitative scoring of papers was applied to their evaluation. Authors of the identified papers were contacted to obtain data on the mentioned co-exposures. A measurement of the biological interaction among two putative risk factors was estimated by the attributable proportion (AP) due to interaction. We identified 13 case-control studies, which included 2066 gastric cancer cases and 2754 controls. Using the random effects model, we found no association between PstI/RsaI genotype and gastric cancer risk [odds ratio (OR) = 0.97 (95% confidence interval (CI): 0.79-1.18) for c2 allele carriers and OR = 1.36 (95% CI: 0.82-2.25) for c2 homozygotes compared with homozygotes wild-type]. When only high-quality scored studies were considered, a statistically significant increased risk appeared among Asians [OR = 1.50 (95% CI: 1.16-1.94) for c2 carriers and OR = 2.62 (95% CI: 1.23-5.57) for c2 homozygotes]. No interaction was detected between CYP2E1-smoking/alcohol (AP = 0), while an AP of 60% appeared for individuals both c2 homozygotes and glutathione S-transferase M1 (GSTM1) null compared with both homozygotes wild-type. This meta-analysis suggests that the CYP2E1 PstI/RsaI polymorphism may be a risk factor for gastric cancer in Asians, and that a synergic relation among GSTM1 and CYP2E1 may account for a proportion of gastric cancer cases. 16837478 71 75 GSTs Gene 373156 16837478 79 93 gastric cancer Disease D013274 16837478 46 65 cytochrome P450 2E1 Gene 1571 16837478 67 73 CYP2E1 Gene 1571 16837478 95 99 PstI Gene 6690 16837478 123 137 gastric cancer Disease D013274 16837478 233 239 CYP2E1 Gene 1571 16837478 265 271 CYP2E1 Gene 1571 16837478 282 296 gastric cancer Disease D013274 16837478 830 844 gastric cancer Disease D013274 16837478 934 938 PstI Gene 6690 16837478 957 971 gastric cancer Disease D013274 16837478 1270 1276 Asians Environment 1571-D013274 16837478 1415 1421 CYP2E1 Gene 1571 16837478 1516 1544 glutathione S-transferase M1 Gene 2944 16837478 1546 1551 GSTM1 Gene 2944 16837478 1637 1643 CYP2E1 Gene 1571 16837478 1644 1648 PstI Gene 6690 16837478 1692 1706 gastric cancer Disease D013274 16837478 1710 1716 Asians Environment 1571-D013274 16837478 1753 1758 GSTM1 Gene 2944 16837478 1763 1769 CYP2E1 Gene 1571 16837478 1802 1816 gastric cancer Disease D013274 12860364|t|Gene-environment interaction in psychiatric disorders as indicated by season of birth variations in tryptophan hydroxylase (TPH), serotonin transporter (5-HTTLPR) and dopamine receptor (DRD4) gene polymorphisms. 12860364|t|Genetic and environmental factors, as well as their interactions, are likely to be involved in psychiatric disorders. Considerable progress has been made in association and linkage studies with various candidate genes, at times with conflicting or ambiguous results. An environmental factor that has persistently shown associations with several psychiatric and neurological disorders is the season of birth. If it is the interaction of a specific gene allele with a specific season of birth that constitutes an increased (or decreased) risk for a disorder, then the individuals with this disorder are likely to have a season of birth variation in this gene allele. We investigated the variations in TPH, 5-HTTLPR and DRD4 gene polymorphisms according to seasonality of birth in 954 patients with unipolar affective disorder, bipolar affective disorder, and schizophrenia, respectively, and in 395 controls. We first analyzed season of birth variations in the gene alleles with one cycle or two cycles per year, and then compared specified birth seasons with each other. We found season of birth variations in these gene alleles that were different for different psychiatric disorders. Significant differences between cases and controls could be obtained when restricting the analysis within certain birth seasons but not within others. Our results thus suggest an interaction between the seasons of birth and the expression of the candidate genes, and that season of birth is a confounding variable when investigating the role of the candidate genes in susceptibility to psychiatric disorders. 12860364 32 53 psychiatric disorders Disease D001523 12860364 186 190 DRD4 Gene 1815 12860364 95 116 psychiatric disorders Disease D001523 12860364 345 356 psychiatric Disease D001523 12860364 361 383 neurological disorders Disease D009422 12860364 717 721 DRD4 Gene 1815 12860364 805 823 affective disorder Disease D019964 12860364 825 851 bipolar affective disorder Disease C567531 12860364 857 870 schizophrenia Disease D012559 12860364 1079 1105 season of birth variations Environment 1815-D011618 12860364 1079 1105 season of birth variations Environment 1815-D001714 12860364 1079 1105 season of birth variations Environment 1815-D003865 12860364 1079 1105 season of birth variations Environment 1815-D012559 12860364 1162 1183 psychiatric disorders Disease D001523 12860364 1291 1312 certain birth seasons Environment 1815-D011618 12860364 1291 1312 certain birth seasons Environment 1815-D001714 12860364 1291 1312 certain birth seasons Environment 1815-D003865 12860364 1291 1312 certain birth seasons Environment 1815-D012559 12860364 1384 1404 the seasons of birth Environment 1815-D011618 12860364 1384 1404 the seasons of birth Environment 1815-D001714 12860364 1384 1404 the seasons of birth Environment 1815-D003865 12860364 1384 1404 the seasons of birth Environment 1815-D012559 12860364 1571 1592 psychiatric disorders Disease D001523 17694420|t|IL6 genotypes and colon and rectal cancer. 17694420|t|Inflammation appears to play a key role in the development of colorectal cancer (CRC). In this study we examine factors involved in the regulation of inflammation and risk of CRC. Data from a multi-center case-control study of colon (N = 1579 cases and N = 1977 controls) and rectal (N = 794 cases and N = 1005 controls) cancer were used to evaluate the association between the rs1800795 and rs1800796 IL6 polymorphisms and CRC. We evaluated the joint effects of IL6 single nucleotide polymorphisms and regular use of aspirin/NSAIDs and vitamin D receptor (VDR) genotype. Having a C allele of the rs1800796 IL6 polymorphisms and the GG genotype of the rs1800795 IL6 polymorphisms was associated with a statistically significantly reduced the risk of colon (OR 0.76 95% CI 0.57, 1.00), but not rectal (OR 1.49 95% CI 1.02,2.16) cancer. Both IL6 polymorphisms were associated with significant interaction with current use of aspirin/NSAIDs to alter risk of colon cancer: individuals with a C allele in either polymorphism who were current users of aspirin/NSAIDs had the lowest colon cancer risk. CRC risk also was associated with an interaction between VDR and IL6 genotypes that was modified by current use of aspirin/NSAIDs. This study provides further support for inflammation-related factors in the etiology of CRC. Other studies are needed to explore other genes in this and other inflammation-related pathways. 17694420 0 3 IL6 Gene 3569 17694420 28 41 rectal cancer Disease D012004 17694420 0 12 Inflammation Disease D007249 17694420 62 79 colorectal cancer Disease D015179 17694420 81 84 CRC Disease D015179 17694420 150 162 inflammation Disease D007249 17694420 175 178 CRC Disease D015179 17694420 321 327 cancer Disease D009369 17694420 402 405 IL6 Gene 3569 17694420 424 427 CRC Disease D015179 17694420 463 466 IL6 Gene 3569 17694420 537 555 vitamin D receptor Gene 7421 17694420 557 560 VDR Gene 7421 17694420 607 610 IL6 Gene 3569 17694420 662 665 IL6 Gene 3569 17694420 827 833 cancer Disease D009369 17694420 840 843 IL6 Gene 3569 17694420 908 937 current use of aspirin/NSAIDs Environment 3569-D003110 17694420 955 967 colon cancer Disease D003110 17694420 1029 1060 current users of aspirin/NSAIDs Environment 3569-D003110 17694420 1076 1088 colon cancer Disease D003110 17694420 1095 1098 CRC Disease D015179 17694420 1152 1155 VDR Gene 7421 17694420 1160 1163 IL6 Gene 3569 17694420 1195 1224 current use of aspirin/NSAIDs Environment 7421-D015179 17694420 1195 1224 current use of aspirin/NSAIDs Environment 3569-D015179 17694420 1266 1278 inflammation Disease D007249 17694420 1314 1317 CRC Disease D015179 17694420 1385 1397 inflammation Disease D007249 22138747|t|Melatonin pathway genes and breast cancer risk among Chinese women. 22138747|t|Previous studies suggest that melatonin may act on cancer growth through a variety of mechanisms, most notably by direct anti-proliferative effects on breast cancer cells and via interactions with the estrogen pathway. Three genes are largely responsible for mediating the downstream effects of melatonin: melatonin receptors 1a and 1b (MTNR1a and MTNR1b), and arylalkylamine N-acetyltransferase (AANAT). It is hypothesized that genetic variation in these genes may lead to altered protein production or function. To address this question, we conducted a comprehensive evaluation of the association between common single nucleotide polymorphisms (SNPs) in the MTNR1a, MTNR1b, and AANAT genes and breast cancer risk among 2,073 cases and 2,083 controls, using a two-stage analysis of genome-wide association data among women of the Shanghai Breast Cancer Study. Results demonstrate two SNPs were consistently associated with breast cancer risk across both study stages. Compared with MTNR1b rs10765576 major allele carriers (GG or GA), a decreased risk of breast cancer was associated with the AA genotype (OR = 0.78, 95% CI = 0.62-0.97, P = 0.0281). Although no overall association was seen in the combined analysis, the effect of MTNR1a rs7665392 was found to vary by menopausal status (P-value for interaction = 0.001). Premenopausal women with the GG genotype were at increased risk for breast cancer compared with major allele carriers (TT or TG) (OR = 1.57, 95% CI = 1.07-2.31, P = 0.020), while postmenopausal women were at decreased risk (OR = 0.58, 95% 0.36-0.95, P = 0.030). No significant breast cancer associations were found for variants in the AANAT gene. These results suggest that common genetic variation in the MTNR1a and 1b genes may contribute to breast cancer susceptibility, and that associations may vary by menopausal status. Given that multiple variants in high linkage disequilibrium with MTNR1b rs76653292 have been associated with altered function or expression of insulin and glucose family members, further research may focus on clarifying this relationship. 22138747 28 41 breast cancer Disease D001943 22138747 51 57 cancer Disease D009369 22138747 151 164 breast cancer Disease D001943 22138747 337 343 MTNR1a Gene 4543 22138747 348 354 MTNR1b Gene 4544 22138747 361 395 arylalkylamine N-acetyltransferase Gene 15 22138747 397 402 AANAT Gene 15 22138747 660 666 MTNR1a Gene 4543 22138747 668 674 MTNR1b Gene 4544 22138747 680 685 AANAT Gene 15 22138747 696 709 breast cancer Disease D001943 22138747 924 937 breast cancer Disease D001943 22138747 983 989 MTNR1b Gene 4544 22138747 1055 1068 breast cancer Disease D001943 22138747 1231 1237 MTNR1a Gene 4543 22138747 1269 1286 menopausal status Environment 4543-D001943 22138747 1322 1341 Premenopausal women Environment 4544-D001943 22138747 1390 1403 breast cancer Disease D001943 22138747 1501 1521 postmenopausal women Environment 4544-D001943 22138747 1599 1612 breast cancer Disease D001943 22138747 1657 1662 AANAT Gene 15 22138747 1728 1734 MTNR1a Gene 4543 22138747 1766 1779 breast cancer Disease D001943 22138747 1830 1847 menopausal status Environment 4543-D001943 22138747 1830 1847 menopausal status Environment 4544-D001943 22138747 1914 1920 MTNR1b Gene 4544 22138747 1992 1999 insulin Gene 3630 18463401|t|CYP1A1, GSTM1, and GSTT1 polymorphisms, smoking, and lung cancer risk in a pooled analysis among Asian populations. 18463401|t|To evaluate the roles of CYP1A1 polymorphisms [Ile 462Val and T 6235C (MspI)] and deletion of GSTM1 and GSTT1 in lung cancer development in Asian populations, a pooled analysis was conducted on 13 existing studies included in Genetic Susceptibility to Environmental Carcinogenesis database. This pooled analysis included 1,971 cases and 2,130 controls. Lung cancer risk was estimated as odds ratios (OR) and 95% confidence intervals (95% CI) using unconditional logistic regression model adjusting for age, sex, and pack-year. The CYP1A1 6235C variant was associated with squamous cell lung cancer (TC versus TT: OR, 1.42; 95% CI, 0.96-2.09; CC versus TT: OR, 1.97; 95% CI, 1.26-3.07; P trend = 0.003). In haplotype analysis, 462Val-6235T and Ile-C haplotypes were associated with lung cancer risk with reference to the Ile-T haplotype (OR, 3.41; 95% CI, 1.78-6.53 and OR, 1.39; 95% CI, 1.12-1.71, respectively). The GSTM1-null genotype increased squamous cell lung cancer risk (OR, 1.36; 95% CI, 1.05-1.77). When the interaction was evaluated with smoking, increasing trend of lung cancer risk as pack-year increased was stronger among those with the CYP1A1 6235 TC/CC genotype compared with those with TT genotype (P interaction = 0.001) and with the GSTM1-null genotype compared with the present type (Pinteraction = 0.08, when no genotype effect with no exposure was assumed). These results suggest that genetic polymorphisms in CYP1A1 and GSTM1 are associated with lung cancer risk in Asian populations. However, further investigation is warranted considering the relatively small sample size when subgroup analyses were done and the lack of environmental exposure data other than smoking. 18463401 0 6 CYP1A1 Gene 1543 18463401 8 13 GSTM1 Gene 2944 18463401 19 24 GSTT1 Gene 2952 18463401 53 64 lung cancer Disease D008175 18463401 25 31 CYP1A1 Gene 1543 18463401 94 99 GSTM1 Gene 2944 18463401 104 109 GSTT1 Gene 2952 18463401 113 124 lung cancer Disease D008175 18463401 226 248 Genetic Susceptibility Disease D020022 18463401 266 280 Carcinogenesis Disease D063646 18463401 353 364 Lung cancer Disease D008175 18463401 531 537 CYP1A1 Gene 1543 18463401 586 597 lung cancer Disease D008175 18463401 781 792 lung cancer Disease D008175 18463401 917 922 GSTM1 Gene 2944 18463401 961 972 lung cancer Disease D008175 18463401 1078 1089 lung cancer Disease D008175 18463401 1098 1117 pack-year increased Environment 2944-D008175 18463401 1098 1117 pack-year increased Environment 1543-D008175 18463401 1152 1158 CYP1A1 Gene 1543 18463401 1253 1258 GSTM1 Gene 2944 18463401 1433 1439 CYP1A1 Gene 1543 18463401 1444 1449 GSTM1 Gene 2944 18463401 1470 1481 lung cancer Disease D008175 17525974|t|Evidence that the COMT(Val158Met) polymorphism moderates sensitivity to stress in psychosis: an experience-sampling study. 17525974|t|Gene-environment interactions involving the catechol-O-methyltransferase Val(158)Met polymorphism (COMT(Val158Met)) have been implicated in the causation of psychosis. Evidence from general population studies suggests that Met/Met subjects are sensitive to stress, a trait associated with psychosis. We hypothesized that the Met allele would moderate the effects of stress on negative affect (NA) in controls, and on NA and psychosis in patients with a psychotic disorder. Thirty-one patients with a psychotic disorder and comorbid cannabis misuse and 25 healthy cannabis users were studied with the experience sampling method (ESM), a structured diary technique assessing current context and emotional and psychotic experiences in daily life. A significant interaction between COMT(Val158Met) genotype and ESM stress in the model of NA was found for patients (interaction chi(2) = 7.4, P = 0.02), but not for controls (interaction chi(2) = 3.8, P = 0.15). In the model of ESM psychosis, a significant interaction between COMT(Val158Met) genotype and ESM stress was also apparent (interaction chi(2) = 11.6, P < 0.01), with Met/Met patients showing the largest increase in psychotic experiences as well as NA in reaction to ESM stress. The findings suggest that the COMT(Val158Met) polymorphism moderates affective and psychotic responses to stress in patients with psychosis, providing evidence for gene-environment interaction mechanisms in the formation of psychotic symptoms. 17525974 18 22 COMT Gene 1312 17525974 72 78 stress Environment 1312-D011618 17525974 82 91 psychosis Disease D011605 17525974 44 72 catechol-O-methyltransferase Gene 1312 17525974 99 103 COMT Gene 1312 17525974 157 166 psychosis Disease D011605 17525974 289 298 psychosis Disease D011605 17525974 424 433 psychosis Disease D011605 17525974 453 471 psychotic disorder Disease D011618 17525974 500 518 psychotic disorder Disease D011618 17525974 707 716 psychotic Disease D011618 17525974 778 782 COMT Gene 1312 17525974 811 817 stress Environment 1312-D011618 17525974 977 986 psychosis Disease D011605 17525974 1022 1026 COMT Gene 1312 17525974 1055 1061 stress Environment 1312-D011618 17525974 1173 1182 psychotic Disease D011618 17525974 1228 1234 stress Environment 1312-D011618 17525974 1266 1270 COMT Gene 1312 17525974 1319 1328 psychotic Disease D011618 17525974 1342 1348 stress Environment 1312-D011618 17525974 1366 1375 psychosis Disease D011605 17525974 1460 1478 psychotic symptoms Disease D011605 20197460|t|Pooled analysis of phosphatidylinositol 3-kinase pathway variants and risk of prostate cancer. 20197460|t|The phosphatidylinositol 3-kinase (PI3K) pathway regulates various cellular processes, including cellular proliferation and intracellular trafficking, and may affect prostate carcinogenesis. Thus, we explored the association between single-nucleotide polymorphisms (SNP) in PI3K genes and prostate cancer. Pooled data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium were examined for associations between 89 SNPs in PI3K genes (PIK3C2B, PIK3AP1, PIK3C2A, PIK3CD, and PIK3R3) and prostate cancer risk in 8,309 cases and 9,286 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. SNP rs7556371 in PIK3C2B was significantly associated with prostate cancer risk [OR(per allele), 1.08 (95% CI, 1.03-1.14); P(trend) = 0.0017] after adjustment for multiple testing (P(adj) = 0.024). Simultaneous adjustment of rs7556371 for nearby SNPs strengthened the association [OR(per allele), 1.21 (95% CI, 1.09-1.34); P(trend) = 0.0003]. The adjusted association was stronger for men who were diagnosed before the age of 65 years [OR(per allele), 1.47 (95% CI, 1.20-1.79); P(trend) = 0.0001] or had a family history [OR(per allele) = 1.57 (95% CI, 1.11-2.23); P(trend) = 0.0114], and was strongest in those with both characteristics [OR(per allele) = 2.31 (95% CI, 1.07-5.07), P-interaction = 0.005]. Increased risks were observed among men in the top tertile of circulating insulin-like growth factor-I (IGF-I) levels [OR(per allele) = 1.46 (95% CI, 1.04-2.06); P(trend) = 0.075]. No differences were observed with disease aggressiveness (Gleason grade >or=8 or stage T(3)/T(4) or fatal). In conclusion, we observed a significant association between PIK3C2B and prostate cancer risk, especially for familial, early-onset disease, which may be attributable to IGF-dependent PI3K signaling. 20197460 19 48 phosphatidylinositol 3-kinase Gene 5293 20197460 78 93 prostate cancer Disease D011471 20197460 4 33 phosphatidylinositol 3-kinase Gene 5293 20197460 35 39 PI3K Gene 5293 20197460 175 189 carcinogenesis Disease D063646 20197460 274 278 PI3K Gene 5293 20197460 289 304 prostate cancer Disease D011471 20197460 448 452 PI3K Gene 5293 20197460 460 467 PIK3C2B Gene 5287 20197460 469 476 PIK3AP1 Gene 118788 20197460 478 485 PIK3C2A Gene 5286 20197460 487 493 PIK3CD Gene 5293 20197460 499 505 PIK3R3 Gene 8503 20197460 511 526 prostate cancer Disease D011471 20197460 681 688 PIK3C2B Gene 5287 20197460 723 738 prostate cancer Disease D011471 20197460 1072 1098 before the age of 65 years Environment 5287-D011471 20197460 1168 1184 a family history Environment 5287-D011471 20197460 1444 1472 insulin-like growth factor-I Gene 3479 20197460 1474 1479 IGF-I Gene 3479 20197460 1593 1607 aggressiveness Disease D001523 20197460 1720 1727 PIK3C2B Gene 5287 20197460 1732 1747 prostate cancer Disease D011471 20197460 1769 1798 familial, early-onset disease Environment 5287-D011471 20197460 1779 1798 early-onset disease Disease 1 20197460 1843 1847 PI3K Gene 5293 23544014|t|Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors. 23544014|t|Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4 x 10(-6)) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1 x 10(-4)). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01-1.16) in nulliparous women and ranged from 1.03 (0.96-1.10) in parous women with one birth to 1.26 (1.16-1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98) in those with an alcohol intake of <20 g/day and 1.45 (1.14-1.85) in those who drank >/= 20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3 x 10(-5)), with a per-allele OR of 1.14 (1.11-1.17) in parous women and 0.98 (0.92-1.05) in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors. 23544014 57 70 breast cancer Disease D001943 23544014 15 37 genetic susceptibility Disease D020022 23544014 68 81 breast cancer Disease D001943 23544014 285 298 breast cancer Disease D001943 23544014 406 420 breast cancers Disease D001943 23544014 1060 1064 LSP1 Gene 4046 23544014 1079 1085 parity Environment 4046-D001943 23544014 1128 1133 CASP8 Gene 841 23544014 1149 1168 alcohol consumption Environment 841-D001943 23544014 1265 1269 LSP1 Gene 4046 23544014 1304 1321 nulliparous women Environment 4046-D001943 23544014 1358 1385 parous women with one birth Environment 4046-D001943 23544014 1420 1440 at least four births Environment 4046-D001943 23544014 1446 1451 CASP8 Gene 841 23544014 1517 1547 an alcohol intake of <20 g/day Environment 841-D001943 23544014 1875 1888 breast cancer Disease D001943 17957785|t|Genetic polymorphisms of MDM2, cumulative cigarette smoking and nonsmall cell lung cancer risk. 17957785|t|Abnormalities of the tumor suppressor TP53 pathway are critical in the development of many cancers since it regulates cell cycle components and apoptosis. Murine double minute-2 (MDM2) protein is a central node in the p53 pathway and a direct negative regulator of p53. The MDM2 SNP309 (rs2279744) polymorphism increases MDM2 RNA and protein levels, attenuating the p53 pathway. The MDM2 SNP309 polymorphism was investigated in 1,787 Caucasian nonsmall cell lung cancer (NSCLC) patients and 1,360 healthy controls. Cases and controls were analyzed for associations with genotype and adjusted for age, gender, histology and smoking history. There were no overall associations between the MDM2 genotypes and risk of lung cancer (adjusted odds ratios [AORs] = 0.82 [95% confidence interval [CI] = 0.6-1.1] for the T/G genotype and AOR = 1.32 [95% CI = 0.9-2.0] for the G/G genotype). A statistically significant interaction (p = 0.01) was found between smoking and MDM2 genotypes. Consistent with this interaction, stratified analysis by pack-years of smoking demonstrated that the AORs of G/G vs. T/T were 1.56 (1.0-2.7), 1.46 (1.0-2.2), 0.80 (0.5-1.3) and 0.63 (0.4-1.1), respectively, for never, mild (<30 pack-years), moderate (30-57 pack-years) and heavy smokers (>or=58 pack-years). In conclusion, a strong gene-smoking interaction was observed between the MDM2 SNP309 and NSCLC risk. 17957785 25 29 MDM2 Gene 4193 17957785 64 89 nonsmall cell lung cancer Disease D002289 17957785 21 26 tumor Disease D009369 17957785 38 42 TP53 Gene 7157 17957785 91 98 cancers Disease D009369 17957785 155 177 Murine double minute-2 Gene 17246 17957785 179 183 MDM2 Gene 17246 17957785 218 221 p53 Gene 22060 17957785 265 268 p53 Gene 22060 17957785 274 278 MDM2 Gene 4193 17957785 321 325 MDM2 Gene 4193 17957785 366 369 p53 Gene 7157 17957785 383 387 MDM2 Gene 4193 17957785 444 469 nonsmall cell lung cancer Disease D002289 17957785 471 476 NSCLC Disease D002289 17957785 687 691 MDM2 Gene 4193 17957785 714 725 lung cancer Disease D008175 17957785 950 957 smoking Environment 4193-D002280 17957785 962 966 MDM2 Gene 4193 17957785 1189 1284 never, mild (<30 pack-years), moderate (30-57 pack-years) and heavy smokers (>or=58 pack-years) Environment 4193-D002280 17957785 1360 1364 MDM2 Gene 4193 17957785 1376 1381 NSCLC Disease D002289 15767330|t|Matrix metalloproteinase-1 promoter polymorphism and lung cancer risk. 15767330|t|Extracellular matrix-degrading matrix metalloproteinase-1 (MMP-1) is an interstitial collagenase that degrades the interstitial types I, II, and III collagens, and overexpression of MMP-1 is associated with cancer development and cellular invasion. The 2G allele of the MMP-1 -1607 1G/2G polymorphism is associated with enhanced transcriptional activity. We investigated the association between the MMP-1 1G/2G polymorphism and lung cancer risk in 1,752 Caucasian lung cancer patients and 1,363 healthy controls. There were no overall associations between the MMP-1 genotypes and risk of lung cancer, with the adjusted odds ratios of 1.15 [95% confidence interval (CI), 0.94-1.40] for the 1G/2G genotype and 1.14 (95% CI, 0.90-1.45) for the 2G/2G genotype, when versus the 1G/1G genotype. Stratified analyses suggested higher lung cancer risk for the 2G allele in never-smokers and males, with the adjusted odds ratios of 1.67 (95% CI, 1.02-2.76; 1G/2G) and 1.50 (95% CI, 0.86-2.62; 2G/2G) in never-smokers; and 1.30 (95% CI, 1.00-1.75; 1G/2G) and 1.23 (95% CI, 0.88-1.73; 2G/2G) in males, respectively. In conclusion, genotypes containing the 2G allele of the MMP-1 polymorphism are associated with higher risk of lung cancer in never-smokers and in males. 15767330 0 26 Matrix metalloproteinase-1 Gene 4312 15767330 53 64 lung cancer Disease D008175 15767330 31 57 matrix metalloproteinase-1 Gene 4312 15767330 59 64 MMP-1 Gene 4312 15767330 182 187 MMP-1 Gene 4312 15767330 207 213 cancer Disease D009369 15767330 270 275 MMP-1 Gene 4312 15767330 399 404 MMP-1 Gene 4312 15767330 428 439 lung cancer Disease D008175 15767330 464 475 lung cancer Disease D008175 15767330 560 565 MMP-1 Gene 4312 15767330 588 599 lung cancer Disease D008175 15767330 826 837 lung cancer Disease D008175 15767330 864 877 never-smokers Environment 4312-D008175 15767330 882 887 males Environment 4312-D008175 15767330 993 1006 never-smokers Environment 4312-D008175 15767330 1083 1088 males Environment 4312-D008175 15767330 1161 1166 MMP-1 Gene 4312 15767330 1215 1226 lung cancer Disease D008175 15767330 1230 1243 never-smokers Environment 4312-D008175 15767330 1251 1256 males Environment 4312-D008175 23306950|t|A genetic variant in miR-146a modifies colorectal cancer susceptibility in a Chinese population. 23306950|t|MicroRNAs (miRNAs) are a family of endogenous, small, noncoding RNA molecules that involved in a wide range of biological processes including differentiation, proliferation, and apoptosis. A polymorphism G>C (rs2910164) is located in the stem region opposite to the mature miR-146a sequence. In our study, we investigated whether rs2910164 is associated with the risk of colorectal cancer (CRC) in a Chinese population. We genotyped the rs2910164 polymorphism using TaqMan method and evaluated the association with CRC risk in a case-control study, including 1,147 CRC patients and 1,203 cancer-free controls. Logistic regression models were used to assess the genetic effects on the development of CRC. Overall, we found that rs2910164 was significantly associated with the reduced CRC risk [GC/CC versus GG: adjusted odds ratio (OR) = 0.78, 95 % confidence intervals (CIs) = 0.66-0.93]. In the stratification analysis, this decreased risk was also pronounced among non-smokers (0.75, 0.61-0.93), non-drinkers (0.77, 0.63-0.94), and no family history of cancer (0.79, 0.65-0.95). Furthermore, GC/CC genotypes were associated with reduced CRC susceptibility in intermediate differentiated CRC (0.75, 0.62-0.90), and similar effect was observed in patients with the advanced stage tumor (Dukes C and D) (0.76, 0.61-0.93). In conclusion, our results suggest that miR-146a rs2910164 may contribute to the susceptibility to CRC in a Chinese population. Further larger population-based prospective and functional studies are needed to validate our findings. 23306950 21 29 miR-146a Gene 406938 23306950 39 56 colorectal cancer Disease D015179 23306950 273 281 miR-146a Gene 406938 23306950 371 388 colorectal cancer Disease D015179 23306950 390 393 CRC Disease D015179 23306950 515 518 CRC Disease D015179 23306950 565 568 CRC Disease D015179 23306950 588 594 cancer Disease D009369 23306950 699 702 CRC Disease D015179 23306950 783 786 CRC Disease D015179 23306950 967 978 non-smokers Environment 406938-D015179 23306950 998 1010 non-drinkers Environment 406938-D015179 23306950 1034 1061 no family history of cancer Environment 406938-D015179 23306950 1055 1061 cancer Disease D009369 23306950 1139 1142 CRC Disease D015179 23306950 1189 1192 CRC Disease D015179 23306950 1261 1285 the advanced stage tumor Environment 406938-D015179 23306950 1280 1285 tumor Disease D009369 23306950 1361 1369 miR-146a Gene 406938 23306950 1420 1423 CRC Disease D015179 20306294|t|GPX1 Pro198Leu polymorphism and breast cancer risk: a meta-analysis. 20306294|t|A genetic polymorphism at codon 198 in the human glutathione peroxidase 1 gene was reported to be associated with several cancers. However, this relationship remains controversial, especially in breast cancer. For better understanding the effect of GPX1 Pro198Leu polymorphism on breast cancer, a meta-analysis was performed. By searching relevant literatures, a total of six case-control studies, containing 5,509 breast cancer cases and 6,542 healthy controls, were included. The strength of association between GPX1 Pro198Leu polymorphism and breast cancer risk was assessed by odds ratio (OR) with the corresponding 95% confidence interval (95%CI). And the results strongly suggested that there was no significant association between variant Leu allele and breast cancer susceptibility in overall comparisons in all genetic models [additive model: OR, 1.04; 95% CI, 0.92-1.18; P = 0.555; dominant model: OR, 1.01; 95% CI, 0.94-1.09; P = 0.777; recessive model: OR, 1.04; 95% CI, 0.92-1.18; P = 0.536]. However in subgroup analysis, an elevated risk in African population with variant Leu allele was revealed in additive (OR, 1.91; 95% CI, 1.02-3.58; P = 0.044) and recessive (OR, 2.09; 95% CI, 1.16-3.76; P = 0.014) genetic model. No apparent association between this polymorphism and different menopausal status (premenopausal and postmenopausal) and the other ethnicities (almost Caucasians) was showed. In conclusion, this meta-analysis strongly suggests that GPX1 Pro198Leu polymorphism is not associated with breast cancer risk in Caucasians, and an elevated risk in Africans needs large-scale investigations to confirm. 20306294 0 4 GPX1 Gene 2876 20306294 32 45 breast cancer Disease D001943 20306294 49 73 glutathione peroxidase 1 Gene 2876 20306294 122 129 cancers Disease D009369 20306294 195 208 breast cancer Disease D001943 20306294 249 253 GPX1 Gene 2876 20306294 280 293 breast cancer Disease D001943 20306294 415 428 breast cancer Disease D001943 20306294 514 518 GPX1 Gene 2876 20306294 546 559 breast cancer Disease D001943 20306294 761 774 breast cancer Disease D001943 20306294 1056 1074 African population Environment 2876-D001943 20306294 1467 1471 GPX1 Gene 2876 20306294 1518 1531 breast cancer Disease D001943 20306294 1576 1584 Africans Environment 2876-D001943 15735051|t|One-carbon metabolism, MTHFR polymorphisms, and risk of breast cancer. 15735051|t|Accumulating evidence from epidemiologic studies suggests that risk of breast cancer is reduced in relation to increased consumption of folate and related B vitamins. We investigated independent and joint effects of B vitamin intake as well as two polymorphisms of a key one-carbon metabolizing gene [i.e., methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C] on breast cancer risk. The study uses the resources of a population-based case-control study, which includes 1,481 cases and 1,518 controls. Significant inverse associations between B vitamin intake and breast cancer risk were observed among non-supplement users. The greatest reduction in breast cancer risk was observed among non-supplement users in the highest quintile of dietary folate intake [odds ratio (OR), 0.61; 95% confidence interval (95% CI), 0.41-0.93] as compared with non-supplement users in the lowest quintile of dietary folate intake (high-risk individuals). The MTHFR 677T variant allele was associated with increased risk of breast cancer (P, trend = 0.03) with a multivariate-adjusted OR of 1.37 (95% CI, 1.06-1.78) for the 677TT genotype. The 1298C variant allele was inversely associated with breast cancer risk (P, trend = 0.03), and was likely due to the linkage of this allele to the low-risk allele of 677C. The MTHFR-breast cancer associations were more prominent among women who did not use multivitamin supplements. Compared with 677CC individuals with high folate intake, elevation of breast cancer risk was most pronounced among 677TT women who consumed the lowest levels of dietary folate (OR, 1.83; 95% CI, 1.13-2.96) or total folate intake (OR, 1.71; 95% CI, 1.08-2.71). From a public heath perspective, it is important to identify risk factors, such as low B vitamin consumption, that may guide an effective prevention strategy against the disease. 15735051 23 28 MTHFR Gene 4524 15735051 56 69 breast cancer Disease D001943 15735051 71 84 breast cancer Disease D001943 15735051 307 342 methylenetetrahydrofolate reductase Gene 4524 15735051 344 349 MTHFR Gene 4524 15735051 374 387 breast cancer Disease D001943 15735051 574 587 breast cancer Disease D001943 15735051 661 674 breast cancer Disease D001943 15735051 953 958 MTHFR Gene 4524 15735051 1017 1030 breast cancer Disease D001943 15735051 1188 1201 breast cancer Disease D001943 15735051 1311 1316 MTHFR Gene 4524 15735051 1317 1330 breast cancer Disease D001943 15735051 1376 1416 who did not use multivitamin supplements Environment 4524-D001943 15735051 1488 1501 breast cancer Disease D001943 15735051 1558 1593 the lowest levels of dietary folate Environment 4524-D001943 15735051 1627 1646 total folate intake Environment 4524-D001943 20393453|t|Interaction of FKBP5 with childhood adversity on risk for post-traumatic stress disorder. 20393453|t|FKBP5 regulates the cortisol-binding affinity and nuclear translocation of the glucocorticoid receptor. Polymorphisms at the FKBP5 locus have been associated with increased recurrence risk of depressive episodes and rapid response to antidepressant treatment. A recent study showed that FKBP5 genotypes moderated the risk of post-traumatic stress disorder (PTSD) symptoms associated with childhood maltreatment. One thousand one hundred forty-three European Americans (EAs) and 1284 African Americans (AAs) recruited for studies of the genetics of substance dependence were also screened for lifetime PTSD. Four single-nucleotide polymorphisms (SNPs) in FKBP5, rs3800373, rs9296158, rs1360780, and rs9470080, were genotyped on the complete sample. Logistic regression analyses were performed to explore the interactive effect of FKBP5 polymorphisms and childhood adversity on the risk for PTSD. After correction for multiple testing, childhood adversity significantly increased the risk for PTSD. FKBP5 genotypes were not associated with the development of the disorder. In AAs, one of the SNPs, rs9470080, moderated the risk of PTSD that was associated with childhood abuse. Without childhood adverse experiences, participants with the TT genotype of this SNP had the lowest risk for PTSD, whereas they had the highest risk for PTSD after childhood adversity exposure. In addition, in EAs, alcohol dependence was observed to interact with childhood adverse experiences, and also FKBP5 polymorphisms, to increase the risk for PTSD. This study provides further evidence of a gene x environment effect of FKBP5 and childhood abuse on the risk for PTSD in AAs. Further study is required in other populations. 20393453 15 20 FKBP5 Gene 2289 20393453 26 45 childhood adversity Environment 2289-D013313 20393453 58 88 post-traumatic stress disorder Disease D013313 20393453 0 5 FKBP5 Gene 2289 20393453 79 102 glucocorticoid receptor Gene 2908 20393453 125 130 FKBP5 Gene 2289 20393453 192 202 depressive Disease D003866 20393453 287 292 FKBP5 Gene 2289 20393453 325 355 post-traumatic stress disorder Disease D013313 20393453 357 361 PTSD Disease D013313 20393453 388 410 childhood maltreatment Environment 2289-D013313 20393453 548 568 substance dependence Disease D019966 20393453 601 605 PTSD Disease D013313 20393453 654 659 FKBP5 Gene 2289 20393453 829 834 FKBP5 Gene 2289 20393453 889 893 PTSD Disease D013313 20393453 991 995 PTSD Disease D013313 20393453 997 1002 FKBP5 Gene 2289 20393453 1129 1133 PTSD Disease D013313 20393453 1159 1174 childhood abuse Environment 2289-D013313 20393453 1285 1289 PTSD Disease D013313 20393453 1329 1333 PTSD Disease D013313 20393453 1340 1368 childhood adversity exposure Environment 2289-D013313 20393453 1391 1409 alcohol dependence Disease D000437 20393453 1391 1409 alcohol dependence Environment 2289-D013313 20393453 1480 1485 FKBP5 Gene 2289 20393453 1526 1530 PTSD Disease D013313 20393453 1603 1608 FKBP5 Gene 2289 20393453 1613 1628 childhood abuse Environment 2289-D013313 20393453 1645 1649 PTSD Disease D013313 17164358|t|Association of genetic variants of O6-methylguanine-DNA methyltransferase with risk of lung cancer in non-Hispanic Whites. 17164358|t|O6-methylguanine, a methylated damage lesion in DNA, correlates with spontaneous G:C --> A:T transition mutations and leads to activation of oncogene K-ras or dysfunction of the tumor suppressor gene p53. O6-methylguanine-DNA methyltransferase (MGMT) is critical for repairing damage to the O6-position of guanine. Therefore, we tested our hypothesis that genetic variants of MGMT are associated with increased lung cancer risk in a Caucasian population of 1,121 lung cancer patients and 1,163 matched cancer-free controls. We genotyped four potentially functional single nucleotide polymorphisms (SNPs) of MGMT: exon 3 codon 84C --> T (L84F), exon 5 codon 143A --> G (I143V), and two promoter SNPs 135G --> T and 485C --> A. The allele frequency distributions of the SNPs of codon 84C --> T and the promoter 135G --> T in the cases were borderline different from that in the controls. After defining the minor allele (T for codon 84C --> T and G for codon 143A --> G) as the variant allele, we categorized the MGMT genotypes as either 0 variants (84CC-143AA) or 1-4 variants. Compared with 0 variants, those with 1-4 variants showed a statistically significantly increased risk of lung cancer (P = 0.040). Further stratification analysis showed that this increased risk was more pronounced in women, current smokers, and non-small cell lung cancer. We did not find any association between the MGMT promoter SNPs and lung cancer risk. Our findings suggest that non-synonymous SNPs in MGMT are associated with modestly increased risk of lung cancer in Caucasians and need to be further investigated. 17164358 35 73 O6-methylguanine-DNA methyltransferase Gene 4255 17164358 87 98 lung cancer Disease D008175 17164358 150 155 K-ras Gene 3845 17164358 178 183 tumor Disease D009369 17164358 200 203 p53 Gene 7157 17164358 205 243 O6-methylguanine-DNA methyltransferase Gene 4255 17164358 245 249 MGMT Gene 4255 17164358 376 380 MGMT Gene 4255 17164358 411 422 lung cancer Disease D008175 17164358 463 474 lung cancer Disease D008175 17164358 502 508 cancer Disease D009369 17164358 607 611 MGMT Gene 4255 17164358 1011 1015 MGMT Gene 4255 17164358 1182 1193 lung cancer Disease D008175 17164358 1294 1299 women Environment 4255-D008175 17164358 1301 1316 current smokers Environment 4255-D008175 17164358 1322 1348 non-small cell lung cancer Disease D002289 17164358 1322 1348 non-small cell lung cancer Environment 4255-D008175 17164358 1394 1398 MGMT Gene 4255 17164358 1417 1428 lung cancer Disease D008175 17164358 1484 1488 MGMT Gene 4255 17164358 1536 1547 lung cancer Disease D008175 20599521|t|The functional IGFBP7 promoter -418G>A polymorphism and risk of head and neck cancer. 20599521|t|Insulin-like growth factor binding protein 7 (IGFBP7) functions mostly independent of the IGF signaling pathway and acts as a tumor suppressor in multiple cancers, but roles of IGFBP7 genetic variants in cancer remains unknown. In a hospital-based study of 1065 patients with squamous cell carcinoma of head and neck (SCCHN) and 1112 cancer-free controls of non-Hispanic whites, we investigated associations between two putatively functional IGFBP7 promoter single nucleotide polymorphisms (SNPs) (-702G>C, rs11573014 and -418G>A, rs4075349) and SCCHN risk. A significantly lower SCCHN risk was observed in those subjects carrying -418AG (adjusted OR=0.82, 95% CI=0.67-0.99) and -418AG+AA (adjusted OR=0.82, 95% CI=0.69-0.99) genotypes than those carrying the -418GG genotype, but not for the -702G>C SNP. However, those subjects carrying two common homozygous genotypes of these two SNPs (-418GG and -702GG) had an increased risk (adjusted OR=1.21, 95% CI=1.00-1.46) than did those carrying variant genotypes (-418AG+AA and -702CG+CC). This increased risk was more evident in subgroups of never smokers and subjects with oral cancer. Further functional analysis showed that the IGFBP7 -418A allele had significantly higher promoter and DNA-protein binding activities than did the G allele, suggesting a tumor suppressor role of this allelic change in the SCCHN etiology. We conclude that the functional variant -418G>C in the IGFBP7 promoter is associated with reduced risk of SCCHN, likely by enhancing the IGFBP7 promoter and DNA-protein binding activities. Larger studies are needed to validate our findings. 20599521 15 21 IGFBP7 Gene 3490 20599521 64 84 head and neck cancer Disease D006258 20599521 0 44 Insulin-like growth factor binding protein 7 Gene 3490 20599521 46 52 IGFBP7 Gene 3490 20599521 126 131 tumor Disease D009369 20599521 155 162 cancers Disease D009369 20599521 177 183 IGFBP7 Gene 3490 20599521 204 210 cancer Disease D009369 20599521 276 299 squamous cell carcinoma Disease D002294 20599521 334 340 cancer Disease D009369 20599521 442 448 IGFBP7 Gene 3490 20599521 1090 1103 never smokers Environment 3490-D009369 20599521 1122 1133 oral cancer Disease D009062 20599521 1122 1133 oral cancer Environment 3490-D009369 20599521 1179 1185 IGFBP7 Gene 3490 20599521 1304 1309 tumor Disease D009369 20599521 1427 1433 IGFBP7 Gene 3490 20599521 1509 1515 IGFBP7 Gene 3490 18195713|t|Serious obstetric complications interact with hypoxia-regulated/vascular-expression genes to influence schizophrenia risk. 18195713|t|The etiology of schizophrenia is thought to include both epistasis and gene-environment interactions. We sought to test whether a set of schizophrenia candidate genes regulated by hypoxia or involved in vascular function in the brain (AKT1, BDNF, CAPON, CHRNA7, COMT, DTNBP1, GAD1, GRM3, NOTCH4, NRG1, PRODH, RGS4, TNF-alpha) interacted with serious obstetric complications to influence risk for schizophrenia. A family-based study of transmission disequilibrium was conducted in 116 trios. Twenty-nine probands had at least one serious obstetric complication (OC) using the McNeil-Sjostrom Scale, and many of the OCs reported were associated with the potential for fetal hypoxia. Analyses were conducted using conditional logistic regression and a likelihood ratio test (LRT) between nested models was performed to assess significance. Of the 13 genes examined, four (AKT1 (three SNPs), BDNF (two SNPs), DTNBP1 (one SNP) and GRM3 (one SNP)) showed significant evidence for gene-by-environment interaction (LRT P-values ranged from 0.011 to 0.037). Although our sample size was modest and the power to detect interactions was limited, we report significant evidence for genes involved in neurovascular function or regulated by hypoxia interacting with the presence of serious obstetric complications to increase risk for schizophrenia. 18195713 0 31 Serious obstetric complications Environment 627-D012559 18195713 0 31 Serious obstetric complications Environment 207-D012559 18195713 0 31 Serious obstetric complications Environment 84062-D012559 18195713 0 31 Serious obstetric complications Environment 2913-D012559 18195713 46 53 hypoxia Disease D000860 18195713 103 116 schizophrenia Disease D012559 18195713 16 29 schizophrenia Disease D012559 18195713 137 150 schizophrenia Disease D012559 18195713 180 187 hypoxia Disease D000860 18195713 235 239 AKT1 Gene 207 18195713 241 245 BDNF Gene 627 18195713 247 252 CAPON Gene 9722 18195713 254 260 CHRNA7 Gene 1139 18195713 262 266 COMT Gene 1312 18195713 268 274 DTNBP1 Gene 84062 18195713 276 280 GAD1 Gene 2571 18195713 282 286 GRM3 Gene 2913 18195713 288 294 NOTCH4 Gene 4855 18195713 296 300 NRG1 Gene 3084 18195713 302 307 PRODH Gene 5625 18195713 309 313 RGS4 Gene 5999 18195713 315 324 TNF-alpha Gene 7124 18195713 396 409 schizophrenia Disease D012559 18195713 666 679 fetal hypoxia Disease D005311 18195713 869 873 AKT1 Gene 207 18195713 888 892 BDNF Gene 627 18195713 905 911 DTNBP1 Gene 84062 18195713 926 930 GRM3 Gene 2913 18195713 1227 1234 hypoxia Disease D000860 18195713 1268 1299 serious obstetric complications Environment 627-D012559 18195713 1268 1299 serious obstetric complications Environment 207-D012559 18195713 1268 1299 serious obstetric complications Environment 84062-D012559 18195713 1268 1299 serious obstetric complications Environment 2913-D012559 18195713 1321 1334 schizophrenia Disease D012559 14633679|t|Joint effect of estrogen receptor beta sequence variants and endogenous estrogen exposure on breast cancer risk in Chinese women. 14633679|t|Long-term estrogen exposure and family history of breast cancer are the two factors that are most consistently found to be associated with breast cancer risk. Sequence variants in genes involved in estrogen synthesis, metabolism, and signal transduction may account, in part, for this observation. Using data and DNA samples from the Shanghai Breast Cancer Study, we tested the hypothesis that sequence variants of the estrogen receptor beta gene (ESR2) may be associated with increased risk for breast cancer, particularly among women who have a high level and long-term endogenous estrogen exposure. Direct sequencing of the ESR2 gene among 30 Chinese women revealed eight sequence variants. Association analysis of six common sequence variants in 1134 cases and 1235 controls provided evidence for positive associations between breast cancer risk and two single nucleotide polymorphisms (SNPs), [C(14206)T and C(33390)G], among postmenopausal women. Evidence of a stronger association was found for SNP [C(33390)G] among women with a long duration (> or =34 years) of menstruation (odds ratio, 2.37; 95% confidence interval, 1.18-4.77). A potential synergistic effect between SNP [C(33390)G] and several steroid sex hormones was observed, and a 3-4-fold elevated risk of breast cancer was found among women with a CG or GG genotype in SNP [C(33390)G] combined with a high level of steroid sex hormone or a low level of sex hormone binding globulin. Our results are consistent with the hypothesis of a joint effect of estrogen receptor beta sequence variants and endogenous estrogen exposure on breast cancer risk. 14633679 16 38 estrogen receptor beta Gene 2100 14633679 61 89 endogenous estrogen exposure Environment 2100-D001943 14633679 93 106 breast cancer Disease D001943 14633679 50 63 breast cancer Disease D001943 14633679 139 152 breast cancer Disease D001943 14633679 419 441 estrogen receptor beta Gene 2100 14633679 448 452 ESR2 Gene 2100 14633679 496 509 breast cancer Disease D001943 14633679 627 631 ESR2 Gene 2100 14633679 831 844 breast cancer Disease D001943 14633679 1035 1083 a long duration (> or =34 years) of menstruation Environment 2100-D001943 14633679 1274 1287 breast cancer Disease D001943 14633679 1368 1403 a high level of steroid sex hormone Environment 2100-D001943 14633679 1407 1450 a low level of sex hormone binding globulin Environment 2100-D001943 14633679 1422 1450 sex hormone binding globulin Gene 6462 14633679 1520 1542 estrogen receptor beta Gene 2100 14633679 1565 1593 endogenous estrogen exposure Environment 2100-D001943 14633679 1597 1610 breast cancer Disease D001943 21037224|t|GSTM1 null and NAT2 slow acetylation genotypes, smoking intensity and bladder cancer risk: results from the New England bladder cancer study and NAT2 meta-analysis. 21037224|t|Associations between bladder cancer risk and NAT2 and GSTM1 polymorphisms have emerged as some of the most consistent findings in the genetic epidemiology of common metabolic polymorphisms and cancer, but their interaction with tobacco use, intensity and duration remain unclear. In a New England population-based case-control study of urothelial carcinoma, we collected mouthwash samples from 1088 of 1171 cases (92.9%) and 1282 of 1418 controls (91.2%) for genotype analysis of GSTM1, GSTT1 and NAT2 polymorphisms. Odds ratios and 95% confidence intervals of bladder cancer among New England Bladder Cancer Study subjects with one or two inactive GSTM1 alleles (i.e. the 'null' genotype) were 1.26 (0.85-1.88) and 1.54 (1.05-2.25), respectively (P-trend = 0.008), compared with those with two active copies. GSTT1 inactive alleles were not associated with risk. NAT2 slow acetylation status was not associated with risk among never (1.04; 0.71-1.51), former (0.95; 0.75-1.20) or current smokers (1.33; 0.91-1.95); however, a relationship emerged when smoking intensity was evaluated. Among slow acetylators who ever smoked at least 40 cigarettes/day, risk was elevated among ever (1.82; 1.14-2.91, P-interaction = 0.07) and current heavy smokers (3.16; 1.22-8.19, P-interaction = 0.03) compared with rapid acetylators in each category; but was not observed at lower intensities. In contrast, the effect of GSTM1-null genotype was not greater among smokers, regardless of intensity. Meta-analysis of the NAT2 associations with bladder cancer showed a highly significant relationship. Findings from this large USA population-based study provided evidence that the NAT2 slow acetylation genotype interacts with tobacco smoking as a function of exposure intensity. 21037224 0 5 GSTM1 Gene 2944 21037224 15 19 NAT2 Gene 10 21037224 70 84 bladder cancer Disease D001749 21037224 120 134 bladder cancer Disease D001749 21037224 145 149 NAT2 Gene 10 21037224 21 35 bladder cancer Disease D001749 21037224 45 49 NAT2 Gene 10 21037224 54 59 GSTM1 Gene 2944 21037224 193 199 cancer Disease D009369 21037224 347 356 carcinoma Disease D002277 21037224 480 485 GSTM1 Gene 2944 21037224 487 492 GSTT1 Gene 2952 21037224 497 501 NAT2 Gene 10 21037224 561 575 bladder cancer Disease D001749 21037224 649 654 GSTM1 Gene 2944 21037224 810 815 GSTT1 Gene 2952 21037224 864 868 NAT2 Gene 10 21037224 1109 1151 who ever smoked at least 40 cigarettes/day Environment 10-D001749 21037224 1408 1413 GSTM1 Gene 2944 21037224 1505 1509 NAT2 Gene 10 21037224 1528 1542 bladder cancer Disease D001749 21037224 1664 1668 NAT2 Gene 10 21037224 1710 1725 tobacco smoking Environment 10-D001749 15743496|t|Haplotype analysis of common variants in the BRCA1 gene and risk of sporadic breast cancer. 15743496|t|INTRODUCTION: Truncation mutations in the BRCA1 gene cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population and account for little of the overall incidence of sporadic breast cancer. METHOD: We used whole-gene resequencing data to select haplotype tagging single nucleotide polymorphisms, and examined the association between common haplotypes of BRCA1 and breast cancer in a nested case-control study in the Nurses' Health Study (1323 cases and 1910 controls). RESULTS: One haplotype was associated with a slight increase in risk (odds ratio 1.18, 95% confidence interval 1.02-1.37). A significant interaction (P = 0.05) was seen between this haplotype, positive family history of breast cancer, and breast cancer risk. Although not statistically significant, similar interactions were observed with age at diagnosis and with menopausal status at diagnosis; risk tended to be higher among younger, pre-menopausal women. CONCLUSIONS: We have described a haplotype in the BRCA1 gene that was associated with an approximately 20% increase in risk of sporadic breast cancer in the general population. However, the functional variant(s) responsible for the association are unclear. 15743496 45 50 BRCA1 Gene 672 15743496 68 90 sporadic breast cancer Disease D001943 15743496 42 47 BRCA1 Gene 672 15743496 93 106 breast cancer Disease D001943 15743496 219 241 sporadic breast cancer Disease D001943 15743496 407 412 BRCA1 Gene 672 15743496 417 430 breast cancer Disease D001943 15743496 715 755 positive family history of breast cancer Environment 672-D001943 15743496 742 755 breast cancer Disease D001943 15743496 761 774 breast cancer Disease D001943 15743496 1031 1036 BRCA1 Gene 672 15743496 1108 1130 sporadic breast cancer Disease D001943 16311244|t|Genotypes and haplotypes of matrix metalloproteinase 1, 3 and 12 genes and the risk of lung cancer. 16311244|t|The MMPs (matrix metalloproteinases) are a family of secreted zinc metalloproteases that degrade the collagens of the extracellular matrix important in tissue remodeling and repair during development and inflammation. We investigated the associations between polymorphisms of MMP-1 (-1607 1G/2G, rs1799750), MMP-3 (-1171 5A/6A, rs3025058), and MMP-12 (-82AG, rs2276109, and 1082A/G, rs652438) and the risk of lung cancer in 2014 Caucasian lung cancer patients and 1323 healthy controls. The results were analyzed using logistic regression models, adjusting for covariates. The four polymorphisms were in Hardy-Weinberg disequilibrium. Except for the 1G-1082A, the other linkage disequilibrium tests between the four MMP polymorphisms were statistically significant (P < 0.001). There was no overall association between individual MMP polymorphism and the risk of lung cancer. The MMP polymorphisms jointly were associated with a non-statistically significant higher risk of lung cancer, with the adjusted odds ratio (AOR) of subjects with 5+ variant alleles versus zero variant allele of 1.31 [95% confidence interval (CI), 0.92-1.88]. Stronger associations were observed in never-smokers and males, with the corresponding AORs of 2.44 (95%CI, 1.10-5.43, P(trend) = 0.04) in never smokers and 1.35 (95%CI, 0.79-2.30, P(trend) = 0.04) in men. In haplotype analysis, the 1G-6A-82A-1082G haplotype was associated with higher risk of lung cancer among never smokers, with the AOR of 3.65 (95%CI, 1.62-8.20) when compared with the most common 1G-5A-82A-1082A haplotype. In conclusion, the combined MMP genotypes and associated haplotypes may be associated with higher risk of lung cancer, particularly among never smokers and men. 16311244 28 54 matrix metalloproteinase 1 Gene 4312 16311244 87 98 lung cancer Disease D008175 16311244 204 216 inflammation Disease D007249 16311244 276 281 MMP-1 Gene 4312 16311244 308 313 MMP-3 Gene 4314 16311244 344 350 MMP-12 Gene 4321 16311244 409 420 lung cancer Disease D008175 16311244 439 450 lung cancer Disease D008175 16311244 863 874 lung cancer Disease D008175 16311244 974 985 lung cancer Disease D008175 16311244 1175 1188 never-smokers Environment 4312-D008175 16311244 1175 1188 never-smokers Environment 4321-D008175 16311244 1175 1188 never-smokers Environment 4314-D008175 16311244 1193 1198 males Environment 4312-D008175 16311244 1193 1198 males Environment 4321-D008175 16311244 1193 1198 males Environment 4314-D008175 16311244 1275 1288 never smokers Environment 4312-D008175 16311244 1275 1288 never smokers Environment 4321-D008175 16311244 1275 1288 never smokers Environment 4314-D008175 16311244 1337 1340 men Environment 4312-D008175 16311244 1337 1340 men Environment 4321-D008175 16311244 1337 1340 men Environment 4314-D008175 16311244 1430 1441 lung cancer Disease D008175 16311244 1448 1461 never smokers Environment 4312-D008175 16311244 1448 1461 never smokers Environment 4321-D008175 16311244 1448 1461 never smokers Environment 4314-D008175 16311244 1671 1682 lung cancer Disease D008175 16311244 1703 1716 never smokers Environment 4312-D008175 16311244 1703 1716 never smokers Environment 4321-D008175 16311244 1703 1716 never smokers Environment 4314-D008175 16311244 1721 1724 men Environment 4312-D008175 16311244 1721 1724 men Environment 4321-D008175 16311244 1721 1724 men Environment 4314-D008175 12516537|t|Genetic and exposure risks for chronic beryllium disease. 12516537|t|Exposure to beryllium results in beryllium sensitization, or development of a beryllium-specific, cell-mediated immune response, in 2% to 19% of exposed individuals. Sensitization usually precedes the development of the scarring lung disease, chronic beryllium disease. The development of granulomatous inflammation in patients with CBD is associated with the production of numerous inflammatory cytokines, including IFN-gamma, IL-2, and TNF-alpha (see Fig. 1). In some individuals this can result in increased granulomatous inflammation and a more severe form of the disease. Although the exposure response relationship in sensitization and disease is nonlinear, in some studies, higher exposures were associated with higher rates of sensitization and CBD. Machinists usually have higher levels of beryllium exposure and increased risk of developing sensitization and disease. The impact of the physicochemical properties of beryllium, such as form, solubility, and particle size, on the risk of sensitization and disease are less well understood. It is clear from numerous studies that genetic susceptibility affects risk of beryllium-related health effects. The role of HLA-DPB1 Glu69 in the proliferative response to beryllium and risk of sensitization has been the most well-studied. Some genes, such as Glu69, are important in the development of an antigen-specific, cell-mediated immune response to beryllium or sensitization, whereas others may be important in the development of beryllium-specific granulomatous inflammation or CBD (see Fig. 1). Two copies of the Glu69 gene may be a disease-specific genetic risk factor. The TNF-alpha -308 A variant is associated with beryllium-stimulated TNF-alpha production, which, in turn, is associated with more severe CBD. Whether the TNF-alpha -308 A is a genetic risk factor in CBD, sensitization, or more severe disease still needs to be determined. It is likely that sensitization and CBD are multigenetic processes, and that these genes interact with exposure to determine risk of disease. Current genetic markers are not ready for clinical use as a screening test for beryllium-related health effects because of the low specificity of the markers and the low prevalence of BeS and CBD. 12516537 39 56 beryllium disease Disease D001607 12516537 220 241 scarring lung disease Disease 1 12516537 251 268 beryllium disease Disease D001607 12516537 303 315 inflammation Disease D007249 12516537 417 426 IFN-gamma Gene 3458 12516537 428 432 IL-2 Gene 3558 12516537 438 447 TNF-alpha Gene 7124 12516537 525 537 inflammation Disease D007249 12516537 1173 1181 HLA-DPB1 Gene 3115 12516537 1521 1533 inflammation Disease D007249 12516537 1635 1644 TNF-alpha Gene 7124 12516537 1679 1688 beryllium Environment 7124-D001607 12516537 1700 1709 TNF-alpha Gene 7124 12516537 1786 1795 TNF-alpha Gene 7124 20541936|t|Alcohol consumption and the risk of breast cancer among BRCA1 and BRCA2 mutation carriers. 20541936|t|Alcohol consumption increases the risk of breast cancer among women in the general population, but its effect on women who carry a BRCA gene mutation is unclear. We conducted a case-control study of 1925 matched pairs of predominantly premenopausal women who carry a BRCA1 or a BRCA2 mutation. Information on current alcohol consumption was obtained from a questionnaire administered during the course of genetic counselling or at the time of enrollment. A modest inverse association between breast cancer and reported current alcohol consumption was observed among women with a BRCA1 mutation (OR = 0.82, 95% CI 0.70-0.96), but not among women with a BRCA2 mutation (OR = 1.00; 95% CI 0.71-1.41). Compared to non-drinkers, exclusive consumption of wine was associated with a significant reduction in the risk of breast cancer among BRCA1 carriers (p-trend = 0.01). Alcohol consumption does not appear to increase breast cancer risk in women carrying a BRCA gene mutation. 20541936 36 49 breast cancer Disease D001943 20541936 56 61 BRCA1 Gene 672 20541936 66 71 BRCA2 Gene 675 20541936 42 55 breast cancer Disease D001943 20541936 131 135 BRCA Gene 672 20541936 267 272 BRCA1 Gene 672 20541936 278 283 BRCA2 Gene 675 20541936 492 505 breast cancer Disease D001943 20541936 519 546 current alcohol consumption Environment 672-D001943 20541936 579 584 BRCA1 Gene 672 20541936 652 657 BRCA2 Gene 675 20541936 724 753 exclusive consumption of wine Environment 672-D001943 20541936 813 826 breast cancer Disease D001943 20541936 833 838 BRCA1 Gene 672 20541936 914 927 breast cancer Disease D001943 20541936 953 957 BRCA Gene 672 19672706|t|Polymorphisms in the BRCA1 and ABCB1 genes modulate menopausal hormone therapy associated breast cancer risk in postmenopausal women. 19672706|t|Menopausal hormone therapy (HT) is associated with an increased breast cancer risk among postmenopausal women. In this study, we investigated genetic effect modification of HT associated breast cancer risk in 3,149 postmenopausal breast cancer patients and 5,489 controls from the two German population-based case-control studies MARIE and GENICA. Twenty-eight polymorphisms of 14 candidate genes including two drug and hormone transporter genes (ABCB1/MDR1 and SHBG), four genes involved in cell cycle regulation (BRCA1, P21/CDKN1A, STK15/AURKA and TP53), six cytokine genes (IGFBP3, IL6, TGFB1, TNF, LTA and IGF1), and two cytokine receptor genes (EGFR and ERBB2) were genotyped using validated methods. Conditional logistic regression was used to assess multiplicative statistical interaction between polymorphisms and duration of estrogen-progestagen therapy and estrogen monotherapy use with regard to breast cancer risk assuming log-additive and co-dominant modes of inheritance. Women homozygous for the major ABCB1_rs2214102_G allele were found to be at a significantly increased breast cancer risk associated with combined estrogen-progestagen therapy [odds ratio (OR) = 1.17, 95% confidence interval (CI) = 1.12-1.23, P (interaction) = 0.022]. Additionally, risk associated with estrogen monotherapy was modified by BRCA1_rs799917. We observed a trend with increasing minor T alleles leading to the highest risk in homozygous carriers of the minor allele [OR (95% CI) = 1.17 (0.98-1.39), 1.06 (0.98-1.14), and 1.02 (0.94-1.11) for homozygous minor, heterozygous, and homozygous major allele carriers, respectively; P (interaction) = 0.032]. Our results suggest that genetic variants in ABCB1 and BRCA1 may modify the effect of HT on postmenopausal breast cancer risk. 19672706 21 26 BRCA1 Gene 672 19672706 31 36 ABCB1 Gene 5243 19672706 52 78 menopausal hormone therapy Environment 5243-D001943 19672706 52 78 menopausal hormone therapy Environment 672-D001943 19672706 90 103 breast cancer Disease D001943 19672706 64 77 breast cancer Disease D001943 19672706 187 200 breast cancer Disease D001943 19672706 230 243 breast cancer Disease D001943 19672706 447 452 ABCB1 Gene 5243 19672706 453 457 MDR1 Gene 5243 19672706 462 466 SHBG Gene 6462 19672706 515 520 BRCA1 Gene 672 19672706 522 525 P21 Gene 1026 19672706 526 532 CDKN1A Gene 1026 19672706 534 539 STK15 Gene 6790 19672706 540 545 AURKA Gene 6790 19672706 550 554 TP53 Gene 7157 19672706 577 583 IGFBP3 Gene 3486 19672706 585 588 IL6 Gene 3569 19672706 590 595 TGFB1 Gene 7040 19672706 597 600 TNF Gene 7124 19672706 610 614 IGF1 Gene 3479 19672706 650 654 EGFR Gene 1956 19672706 659 664 ERBB2 Gene 2064 19672706 907 920 breast cancer Disease D001943 19672706 1017 1022 ABCB1 Gene 5243 19672706 1088 1101 breast cancer Disease D001943 19672706 1123 1160 combined estrogen-progestagen therapy Environment 5243-D001943 19672706 1289 1309 estrogen monotherapy Environment 672-D001943 19672706 1326 1331 BRCA1 Gene 672 19672706 1696 1701 ABCB1 Gene 5243 19672706 1706 1711 BRCA1 Gene 672 19672706 1737 1739 HT Environment 5243-D001943 19672706 1737 1739 HT Environment 672-D001943 19672706 1758 1771 breast cancer Disease D001943 19074884|t|Interaction between single nucleotide polymorphisms in selenoprotein P and mitochondrial superoxide dismutase determines prostate cancer risk. 19074884|t|Selenium may affect prostate cancer risk via its plasma carrier selenoprotein P which shows dramatically reduced expression in prostate cancer tumors and cell lines. The selenoprotein P (SEPP1) Ala234 single nucleotide polymorphism (SNP) allele is associated with lower plasma selenoprotein P in men, reducing the concentration/activity of other antioxidant selenoproteins. Selenium status also modifies the effect of the mitochondrial superoxide dismutase (SOD2) SNP Ala16Val on prostate cancer risk. We investigated the relationship of these SNPs with prostate cancer risk. DNA from 2,975 cases and 1,896 age-matched controls from the population-based Prostate Cancer in Sweden study were genotyped using TaqMan assays. Cases were designated aggressive or nonaggressive prostate cancers at diagnosis by clinical criteria. Association with prostate cancer was investigated by logistic regression; gene-gene interaction using a general linear model. The mean plasma selenium concentration measured in 169 controls was relatively low (76.0 +/- 17.2 microg/L). SNP genotype distributions were in Hardy-Weinberg equilibrium. SOD2-Ala16+ men were at a greater risk of prostate cancer [odds ratios (OR), 1.19; 95% confidence intervals (CI), 1.03-1.37] compared with SOD2-Val16 homozygotes. Men homozygous for SEPP1-Ala234 who were also SOD2-Ala16+ had a higher risk of prostate cancer (OR, 1.43; 95% CI, 1.17-1.76) and aggressive prostate cancer (OR, 1.60; 95% CI, 1.22-2.09) than those who were SOD2-Val16 homozygotes (interaction, prostate cancer P = 0.05; aggressive prostate cancer P = 0.01). This interaction was stronger in ever-smokers: SOD2-Ala16+ men homozygous for SEPP1-Ala234 had an almost doubled risk of prostate cancer (OR, 1.97; 95% CI, 1.33-2.91; interaction P = 0.001). In a low-selenium population, SOD2-Ala16+ men homozygous for SEPP1-Ala234 are at an increased risk of prostate cancer/aggressive prostate cancer especially if ever-smokers, because they are likely to produce more mitochondrial H(2)O(2) that they cannot remove, thereby promoting prostate tumor cell proliferation and migration. 19074884 121 136 prostate cancer Disease D011471 19074884 20 35 prostate cancer Disease D011471 19074884 127 142 prostate cancer Disease D011471 19074884 143 149 tumors Disease D009369 19074884 187 192 SEPP1 Gene 6414 19074884 458 462 SOD2 Gene 6648 19074884 480 495 prostate cancer Disease D011471 19074884 554 569 prostate cancer Disease D011471 19074884 654 669 Prostate Cancer Disease D011471 19074884 772 788 prostate cancers Disease D011471 19074884 850 856 cancer Disease D009369 19074884 1122 1126 SOD2 Gene 6648 19074884 1173 1179 cancer Disease D009369 19074884 1261 1265 SOD2 Gene 6648 19074884 1304 1309 SEPP1 Gene 6414 19074884 1331 1335 SOD2 Gene 6648 19074884 1373 1379 cancer Disease D009369 19074884 1434 1440 cancer Disease D009369 19074884 1491 1495 SOD2 Gene 6648 19074884 1537 1543 cancer Disease D009369 19074884 1574 1580 cancer Disease D009369 19074884 1625 1637 ever-smokers Environment 6414-C565201 19074884 1625 1637 ever-smokers Environment 6414-D001471 19074884 1625 1637 ever-smokers Environment 6648-D011471 19074884 1625 1637 ever-smokers Environment 6648-C565201 19074884 1639 1643 SOD2 Gene 6648 19074884 1670 1675 SEPP1 Gene 6414 19074884 1722 1728 cancer Disease D009369 19074884 1813 1817 SOD2 Gene 6648 19074884 1844 1849 SEPP1 Gene 6414 19074884 1894 1900 cancer Disease D009369 19074884 1921 1927 cancer Disease D009369 19074884 1942 1954 ever-smokers Environment 6414-C565201 19074884 1942 1954 ever-smokers Environment 6414-D001471 19074884 1942 1954 ever-smokers Environment 6648-D011471 19074884 1942 1954 ever-smokers Environment 6648-C565201 19074884 2071 2076 tumor Disease D009369 19672705|t|Postmenopausal estrogen monotherapy-associated breast cancer risk is modified by CYP17A1_-34_T>C polymorphism. 19672705|t|Long-term hormone therapy (HT) is a recognized risk factor for postmenopausal breast cancer. Elevated steroid hormone levels play a critical role in breast carcinogenesis and this may be contributed by the efficiency of hormone biosynthesis. Within this context, genetic polymorphisms related to steroid hormone biosynthesis may modify HT-associated postmenopausal breast cancer risk. CYP17 is a key player of this pathway and the CYP17A1_-34_T > C polymorphism has been suggested to affect breast cancer risk in women using long-term HT. We genotyped 13 polymorphisms of seven genes of the steroid hormone biosynthesis pathway in 3,149 postmenopausal breast cancer patients and 5,489 age-matched controls from Germany. We observed a significant interaction of CYP17A1_-34_T > C and HT use on breast cancer risk in a co-dominant model (P (interaction) = 0.007). Current users of estrogen monotherapy showed a significantly increased risk for duration of use per 5-year increment when they were carriers of the CYP17A1_-34_TC genotype (OR 1.13, 95% CI: 1.04-1.23 per 5 years of use). We conclude that CYP17A1_-34_T > C may be part of the genetic background to contribute to postmenopausal breast cancer risk in women using estrogen monotherapy. 19672705 0 35 Postmenopausal estrogen monotherapy Environment 1586-D001943 19672705 47 60 breast cancer Disease D001943 19672705 81 86 CYP17 Gene 1586 19672705 78 91 breast cancer Disease D001943 19672705 156 170 carcinogenesis Disease D063646 19672705 365 378 breast cancer Disease D001943 19672705 385 390 CYP17 Gene 1586 19672705 491 504 breast cancer Disease D001943 19672705 652 665 breast cancer Disease D001943 19672705 783 789 HT use Environment 1586-D001943 19672705 793 806 breast cancer Disease D001943 19672705 862 899 Current users of estrogen monotherapy Environment 1586-D001943 19672705 1188 1201 breast cancer Disease D001943 19672705 1216 1242 using estrogen monotherapy Environment 1586-D001943 16212676|t|Development of depression: sex and the interaction between environment and a promoter polymorphism of the serotonin transporter gene. 16212676|t|Previous research has demonstrated that a polymorphism in the serotonin transporter gene (5-HTTLPR) and adverse psychosocial circumstances interact to predict depression. The purpose of the present study was to explore the extent to which sex modulates these effects. Eighty-one boys and 119 girls (16-19 years old) were interviewed about psychosocial background variables and genotyped for the 5-HTT promoter polymorphism. There were two main results. First, boys and girls carrying the short 5-HTTLPR allele react to different kinds of environmental factors. Whereas males were affected by living in public housing rather than in own owned homes and by living with separated parents, females were affected by traumatic conflicts within the family. Second, the responses of males and females carrying the short 5-HTTLPR allele to environmental stress factors go in opposite directions. Thus, whereas females tend to develop depressive symptoms, males seem to be protected from depression. The results suggest that both the molecular and the psychosocial mechanisms underlying depression may differ between boys and girls. 16212676 15 25 depression Disease D003866 16212676 106 127 serotonin transporter Gene 6532 16212676 62 83 serotonin transporter Gene 6532 16212676 90 98 5-HTTLPR Gene 6532 16212676 104 138 adverse psychosocial circumstances Environment 6532-D003866 16212676 159 169 depression Disease D003866 16212676 395 400 5-HTT Gene 6532 16212676 494 502 5-HTTLPR Gene 6532 16212676 711 720 traumatic Disease D014947 16212676 711 748 traumatic conflicts within the family Environment 6532-D003866 16212676 812 820 5-HTTLPR Gene 6532 16212676 925 944 depressive symptoms Disease D003866 16212676 978 988 depression Disease D003866 16212676 1077 1087 depression Disease D003866 20806441|t|Relationship between genetic polymorphisms of ALDH2 and ADH1B and esophageal cancer risk: a meta-analysis. 20806441|t|AIM: To evaluate the contribution of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) polymorphisms to the risk of esophageal cancer. METHODS: Nineteen articles were included by searching MEDLINE, EMBASE and the Chinese Biomedical Database, 13 on ADH1B and 18 on ALDH2. We performed a meta-analysis of case-control studies including 13 studies on ADH1B (cases/controls: 2390/7100) and 18 studies on ALDH2 (2631/6030). RESULTS: The crude odds ratio [OR (95% confidence interval)] was 2.91 (2.04-4.14) for ADH1B*1/*1 (vs ADH1B*2/*2) and 1.32 (1.17-1.49) for ADH1B*1/*2. The crude OR for ALDH2*1/*2 (vs ALDH2*1/*1) was 2.52 (1.76-3.61). ADH1B*1/*1 increased the risk of esophageal cancer among never/rare [1.56 (0.93-2.61)], moderate [2.71 (1.37-5.35)], and heavy drinkers [3.22 (2.27-4.57)]. ADH1B*1/*2 was associated with a modest risk among moderate drinkers [1.43 (1.09-1.87)]. ALDH2*1/*2 increased the risk among never/rare [1.28 (0.91-1.80)], moderate [3.12 (1.95-5.01)], and heavy [7.12 (4.67-10.86)] drinkers, and among ex-drinkers [5.64 (1.57-20.25)]. ALDH2*2/*2 increased the risk among drinkers [4.42 (1.72-11.36)]. ADH1B*1/*1 plus ALDH2*1/*2 was associated with the highest risk for heavy drinkers [12.45 (2.9-53.46)]. The results of the meta-regression analysis showed that the effects of ADH1B*1/*1 and ALDH2*1/*2 increased with the level of alcohol consumption. ALDH2*1/*2 was associated with a high risk among Taiwan Chinese and Japanese drinkers, as opposed to a moderate risk among drinkers in high-incidence regions of Mainland China. ADH1B*1/*1 in heavy drinkers and ALDH2*1/*2 in moderate-to-heavy drinkers was associated with similarly high risk among both men and women. CONCLUSION: ADH1B/ALDH2 genotypes affect the risk of esophageal cancer, and the risk is modified by alcohol consumption, ethnicity, and gender. 20806441 46 51 ALDH2 Gene 217 20806441 56 61 ADH1B Gene 125 20806441 66 83 esophageal cancer Disease D004938 20806441 37 61 alcohol dehydrogenase-1B Gene 125 20806441 63 68 ADH1B Gene 125 20806441 74 98 aldehyde dehydrogenase-2 Gene 217 20806441 100 105 ALDH2 Gene 217 20806441 136 153 esophageal cancer Disease D004938 20806441 268 273 ADH1B Gene 125 20806441 284 289 ALDH2 Gene 217 20806441 368 373 ADH1B Gene 125 20806441 420 425 ALDH2 Gene 217 20806441 525 530 ADH1B Gene 125 20806441 540 545 ADH1B Gene 125 20806441 577 582 ADH1B Gene 125 20806441 606 611 ALDH2 Gene 217 20806441 621 626 ALDH2 Gene 217 20806441 655 660 ADH1B Gene 125 20806441 688 705 esophageal cancer Disease D004938 20806441 811 816 ADH1B Gene 125 20806441 862 879 moderate drinkers Environment 125-D004938 20806441 900 905 ALDH2 Gene 217 20806441 1079 1084 ALDH2 Gene 217 20806441 1115 1123 drinkers Environment 217-D004938 20806441 1145 1150 ADH1B Gene 125 20806441 1161 1166 ALDH2 Gene 217 20806441 1213 1227 heavy drinkers Environment 217-D004938 20806441 1213 1227 heavy drinkers Environment 125-D004938 20806441 1320 1325 ADH1B Gene 125 20806441 1335 1340 ALDH2 Gene 217 20806441 1361 1393 the level of alcohol consumption Environment 217-D004938 20806441 1361 1393 the level of alcohol consumption Environment 125-D004938 20806441 1395 1400 ALDH2 Gene 217 20806441 1444 1480 Taiwan Chinese and Japanese drinkers Environment 217-D004938 20806441 1572 1577 ADH1B Gene 125 20806441 1586 1600 heavy drinkers Environment 125-D004938 20806441 1605 1610 ALDH2 Gene 217 20806441 1619 1645 moderate-to-heavy drinkers Environment 217-D004938 20806441 1724 1729 ADH1B Gene 125 20806441 1730 1735 ALDH2 Gene 217 20806441 1765 1782 esophageal cancer Disease D004938 20806441 1812 1831 alcohol consumption Environment 217-D004938 20806441 1812 1831 alcohol consumption Environment 125-D004938 20806441 1833 1842 ethnicity Environment 217-D004938 19892796|t|Genetic polymorphisms in the PTPN13 gene and risk of squamous cell carcinoma of head and neck. 19892796|t|Fas-associated phosphatase-1 is encoded by the protein tyrosine phosphatase, non-receptor type 13 (PTPN13) gene and attributes to the resistance to Fas-mediated apoptosis in several tumors, including squamous cell carcinoma of the head and neck (SCCHN). However, no epidemiological studies have investigated the roles of PTPN13 polymorphisms in SCCHN risk. In this hospital-based case-control study of 1069 SCCHN patients and 1102 non-Hispanic white cancer-free controls, we evaluated the associations between three single-nucleotide polymorphisms c.4068 T>G F1356L (rs10033029), c.4566 A>G I1522M (rs2230600) and c.6241 T>G Y2081D (rs989902) located in the coding region of PTPN13 and SCCHN risk. We found that a significantly increased SCCHN risk was associated with the c.4566 I1522M GG genotype [odds ratio (OR), 1.89; 95% confidence interval (CI), 1.27-2.79] and c.6241 Y2081D GT genotype (OR, 1.26; 95% CI, 1.03-1.53) compared with the c.4566 I1522M AA and c.6241 Y2081D TT genotypes, respectively. Further stratified analyses showed that risk associated with the c.4566 I1522M GG genotype was more profound in the subgroups of young (< or = 57 years), males, never smokers, current drinkers and patients with pharyngeal cancer; that risk associated with c.6241 Y2081D GT genotype persisted in subgroups of old (>57 years), males, current drinkers and patients with pharyngeal and laryngeal cancers and that risk associated with c.6241 Y2081D GG genotype was borderline in patients with laryngeal cancer. In conclusion, polymorphisms in the PTPN13 coding region may be biomarkers for susceptibility to SCCHN in USA populations. 19892796 29 35 PTPN13 Gene 5783 19892796 53 76 squamous cell carcinoma Disease D002294 19892796 47 97 protein tyrosine phosphatase, non-receptor type 13 Gene 5783 19892796 99 105 PTPN13 Gene 5783 19892796 182 188 tumors Disease D009369 19892796 200 244 squamous cell carcinoma of the head and neck Disease C535575 19892796 246 251 SCCHN Disease C535575 19892796 321 327 PTPN13 Gene 5783 19892796 345 350 SCCHN Disease C535575 19892796 407 412 SCCHN Disease C535575 19892796 450 456 cancer Disease D009369 19892796 548 554 c.4068 Gene 1035767 19892796 580 586 c.4566 Gene 1039641 19892796 675 681 PTPN13 Gene 5783 19892796 686 691 SCCHN Disease C535575 19892796 738 743 SCCHN Disease C535575 19892796 773 779 c.4566 Gene 1039641 19892796 942 948 c.4566 Gene 1039641 19892796 1070 1076 c.4566 Gene 1039641 19892796 1117 1157 the subgroups of young (< or = 57 years) Environment 5783-C535575 19892796 1159 1164 males Environment 5783-C535575 19892796 1166 1179 never smokers Environment 5783-C535575 19892796 1181 1197 current drinkers Environment 5783-C535575 19892796 1202 1233 patients with pharyngeal cancer Environment 5783-C535575 19892796 1216 1233 pharyngeal cancer Disease D010610 19892796 1300 1328 subgroups of old (>57 years) Environment 5783-C535575 19892796 1330 1335 males Environment 5783-C535575 19892796 1337 1353 current drinkers Environment 5783-C535575 19892796 1358 1404 patients with pharyngeal and laryngeal cancers Environment 5783-C535575 19892796 1387 1404 laryngeal cancers Disease D007822 19892796 1479 1509 patients with laryngeal cancer Environment 5783-C535575 19892796 1503 1509 cancer Disease D009369 19892796 1547 1553 PTPN13 Gene 5783 19892796 1608 1613 SCCHN Disease C535575 21702935|t|Genetic variants in the MRPS30 region and postmenopausal breast cancer risk. 21702935|t|BACKGROUND: Genome-wide association studies have identified several genomic regions that are associated with breast cancer risk, but these provide an explanation for only a small fraction of familial breast cancer aggregation. Genotype by environment interactions may contribute further to such explanation, and may help to refine the genomic regions of interest. METHODS: We examined genotypes for 4,988 SNPs, selected from recent genome-wide studies, and four randomized hormonal and dietary interventions among 2,166 women who developed invasive breast cancer during the intervention phase of the Women's Health Initiative (WHI) clinical trial (1993 to 2005), and one-to-one matched controls. These SNPs derive from 3,224 genomic regions having pairwise squared correlation (r2) between adjacent regions less than 0.2. Breast cancer and SNP associations were identified using a test statistic that combined evidence of overall association with evidence for SNPs by intervention interaction. RESULTS: The combined 'main effect' and interaction test led to a focus on two genomic regions, the fibroblast growth factor receptor two (FGFR2) and the mitochondrial ribosomal protein S30 (MRPS30) regions. The ranking of SNPs by significance level, based on this combined test, was rather different from that based on the main effect alone, and drew attention to the vicinities of rs3750817 in FGFR2 and rs7705343 in MRPS30. Specifically, rs7705343 was included with several FGFR2 SNPs in a group of SNPs having an estimated false discovery rate < 0.05. In further analyses, there were suggestions (nominal P < 0.05) that hormonal and dietary intervention hazard ratios varied with the number of minor alleles of rs7705343. CONCLUSIONS: Genotype by environment interaction information may help to define genomic regions relevant to disease risk. Combined main effect and intervention interaction analyses raise novel hypotheses concerning the MRPS30 genomic region and the effects of hormonal and dietary exposures on postmenopausal breast cancer risk. 21702935 24 30 MRPS30 Gene 10884 21702935 57 70 breast cancer Disease D001943 21702935 109 122 breast cancer Disease D001943 21702935 191 213 familial breast cancer Disease D001943 21702935 549 562 breast cancer Disease D001943 21702935 822 835 Breast cancer Disease D001943 21702935 1133 1138 FGFR2 Gene 2263 21702935 1148 1183 mitochondrial ribosomal protein S30 Gene 10884 21702935 1185 1191 MRPS30 Gene 10884 21702935 1390 1395 FGFR2 Gene 2263 21702935 1413 1419 MRPS30 Gene 10884 21702935 1471 1476 FGFR2 Gene 2263 21702935 1618 1665 hormonal and dietary intervention hazard ratios Environment 10884-D001943 21702935 1939 1945 MRPS30 Gene 10884 21702935 1980 2010 hormonal and dietary exposures Environment 10884-D001943 21702935 2029 2042 breast cancer Disease D001943 21895720|t|Alcohol dehydrogenase-1B Arg47His polymorphism and upper aerodigestive tract cancer risk: a meta-analysis including 24,252 subjects. 21895720|t|BACKGROUND: Cancers of the upper aerodigestive tract (UADT) include malignant tumors of the oral cavity, pharynx, larynx, and esophagus, account for approximately 4% of all new cancers in world. Alcohol drinking is an established risk factor for UADT cancers, and the rate of alcohol metabolism could significantly been influenced by genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) His47Arg (rs1229984). To evaluate whether combined evidence shows ADH1B His47Arg as a common genetic variant that influenced the risk of UADT cancers, we considered all available studies in a meta-analysis. METHODS: Eighteen studies were combined representing data of 8,539 cases and 15,713 controls for meta-analysis. Stratified analyses were carried out to determine the gene-environment interaction between ADH1B His47Arg and alcohol drinking and gene-gene interaction between ADH1B His47Arg and aldehyde dehydrogenase-2 (ALDH2) Glu/Lys related to UADT cancer risk. Potential sources of heterogeneity between studies were explored; sensitivity analysis and publication bias was also evaluated. RESULTS: The ADH1B 47Arg allele was found to be associated with increased risk of UADT cancers, the pooled odds ratios (ORs) being 1.66 (95% CI: 1.54 to 1.79) and 3.47 (95% CI: 2.76 to 4.36) for the His/Arg and Arg/Arg genotypes compared with the His/His genotype, respectively. An 18.48-fold increase in OR (95% CI: 12.95 to 26.40) for UADT cancers among alcohol drinkers with Arg/Arg genotype was found, when compared among nondrinkers with the His/His genotype. Significant interaction between carriers with ADH1B 47Arg and ALDH2 487Lys allele related to risk for UADT cancers was more evident, compared with noncarriers (OR = 10.31, 95% CI: 5.45 to 18.85). CONCLUSIONS: ADH1B 47Arg allele is a common genetic variant that increased the risk of UADT cancers; furthermore, it modulates the susceptibility to UADT cancers coupled with alcohol drinking and interaction with the ALDH2 487Lys allele. 21895720 0 24 Alcohol dehydrogenase-1B Gene 125 21895720 77 83 cancer Disease D009369 21895720 12 19 Cancers Disease D009369 21895720 68 84 malignant tumors Disease D018198 21895720 177 184 cancers Disease D009369 21895720 251 258 cancers Disease D009369 21895720 359 383 alcohol dehydrogenase-1B Gene 125 21895720 385 390 ADH1B Gene 125 21895720 458 463 ADH1B Gene 125 21895720 534 541 cancers Disease D009369 21895720 802 807 ADH1B Gene 125 21895720 872 877 ADH1B Gene 125 21895720 891 915 aldehyde dehydrogenase-2 Gene 217 21895720 917 922 ALDH2 Gene 217 21895720 948 954 cancer Disease D009369 21895720 1102 1107 ADH1B Gene 125 21895720 1176 1183 cancers Disease D009369 21895720 1431 1438 cancers Disease D009369 21895720 1445 1461 alcohol drinkers Environment 125-D009369 21895720 1600 1605 ADH1B Gene 125 21895720 1616 1621 ALDH2 Gene 217 21895720 1661 1668 cancers Disease D009369 21895720 1763 1768 ADH1B Gene 125 21895720 1842 1849 cancers Disease D009369 21895720 1904 1911 cancers Disease D009369 21895720 1925 1941 alcohol drinking Environment 125-D009369 21895720 1967 1972 ALDH2 Gene 217 21073668|t|COMT Val158Met-stress interaction in psychosis: role of background psychosis risk. 21073668|t|BACKGROUND: The interplay between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and environmental stress may have etiological relevance for psychosis, but differential effects have been reported in healthy control and patient groups, suggesting that COMT Val158Met interactions with stress may be conditional on background genetic risk for psychotic disorder. METHODS: Patients with a nonaffective psychotic disorder (n = 86) and control participants (n = 109) were studied with the experience sampling method (a structured diary technique) in order to assess stress, negative affect and momentary psychotic symptoms in the flow of daily life. RESULTS: Multilevel analyses revealed significant three-way interactions between group status (patient or control), COMT genotype and stress in the model of negative affect (chi(2)(2) = 13.26, P < 0.01) as well as in the model of momentary psychotic symptoms (chi(2)(2) = 6.92, P < 0.05). Exploration of the three-way interaction revealed that in patients, COMT genotype moderated the association between stress and negative affect (chi(2)(4) = 11.50, P < 0.005), as well as the association between stress and momentary psychosis (chi(2)(4) = 12.79, P < 0.005). Met/Met genotype patients showed significantly increased psychotic and affective reactivity to stress in comparison to the Val/Met and Val/Val genotypes. In contrast, healthy controls did not display large or significant COMT Val158Met X stress interactions. CONCLUSIONS: Important differences exist in the effect of COMT Val158Met on stress reactivity, which may depend on background risk for psychotic disorder. Differential sensitivity to environmental stress occasioned by COMT Val158Met may be contingent on higher order interactions with genetic variation underlying psychotic disorder. 21073668 0 4 COMT Gene 1312 21073668 37 46 psychosis Disease D011605 21073668 67 76 psychosis Disease D011605 21073668 38 66 catechol-O-methyltransferase Gene 1312 21073668 68 72 COMT Gene 1312 21073668 157 166 psychosis Disease D011605 21073668 267 271 COMT Gene 1312 21073668 357 375 psychotic disorder Disease D011618 21073668 415 433 psychotic disorder Disease D011618 21073668 615 633 psychotic symptoms Disease D011605 21073668 777 781 COMT Gene 1312 21073668 795 801 stress Environment 1312-D011618 21073668 901 919 psychotic symptoms Disease D011605 21073668 1018 1022 COMT Gene 1312 21073668 1066 1072 stress Environment 1312-D011618 21073668 1181 1190 psychosis Disease D011605 21073668 1280 1289 psychotic Disease D011618 21073668 1318 1324 stress Environment 1312-D011618 21073668 1444 1448 COMT Gene 1312 21073668 1540 1544 COMT Gene 1312 21073668 1558 1575 stress reactivity Environment 1312-D011618 21073668 1617 1635 psychotic disorder Disease D011618 21073668 1665 1685 environmental stress Environment 1312-D011618 21073668 1700 1704 COMT Gene 1312 21073668 1796 1814 psychotic disorder Disease D011618 18483851|t|Smoking and the risk of breast cancer in BRCA1 and BRCA2 carriers: an update. 18483851|t|Among women with a mutation in BRCA1 or BRCA2, the risk of breast cancer is high, but it may be modified by exogenous and endogenous factors. There is concern that exposure to carcinogens in cigarette smoke may increase the risk of cancer in mutation carriers. We conducted a matched case-control study of 2,538 cases of breast cancer among women with a BRCA1 (n = 1,920) or a BRCA2 (n = 618) mutation. One non-affected mutation carrier control was selected for each case, matched on mutation, country of birth, and year of birth. Odds ratios were calculated using conditional logistic regression, adjusted for oral contraceptive use and parity. Ever-smoking was not associated with an increased breast cancer risk among BRCA1 carriers (OR = 1.09; 95% CI 0.95-1.24) or among BRCA2 carriers (OR = 0.81; 95% CI 0.63-1.05). The result did not differ when cases were restricted to women who completed the questionnaire within two years of diagnosis. A modest, but significant increase in risk was seen among BRCA1 carriers with a past history of smoking (OR = 1.27; 95% CI 1.06-1.50), but not among current smokers (OR = 0.95; 0.81-1.12). There appears to be no increase in the risk of breast cancer associated with current smoking in BRCA1 or BRCA2 carriers. There is a possibility of an increased risk of breast cancer among BRCA1 carriers associated with past smoking. There may be different effects of carcinogens in BRCA mutation carriers, depending upon the timing of exposure. 18483851 24 37 breast cancer Disease D001943 18483851 41 46 BRCA1 Gene 672 18483851 51 56 BRCA2 Gene 675 18483851 31 36 BRCA1 Gene 672 18483851 40 45 BRCA2 Gene 675 18483851 59 72 breast cancer Disease D001943 18483851 232 238 cancer Disease D009369 18483851 321 334 breast cancer Disease D001943 18483851 354 359 BRCA1 Gene 672 18483851 377 382 BRCA2 Gene 675 18483851 696 709 breast cancer Disease D001943 18483851 721 726 BRCA1 Gene 672 18483851 775 780 BRCA2 Gene 675 18483851 1004 1009 BRCA1 Gene 672 18483851 1025 1050 a past history of smoking Environment 672-D001943 18483851 1183 1196 breast cancer Disease D001943 18483851 1232 1237 BRCA1 Gene 672 18483851 1241 1246 BRCA2 Gene 675 18483851 1304 1317 breast cancer Disease D001943 18483851 1324 1329 BRCA1 Gene 672 18483851 1355 1367 past smoking Environment 672-D001943 19318433|t|Nucleotide excision repair pathway polymorphisms and pancreatic cancer risk: evidence for role of MMS19L. 19318433|t|BACKGROUND: Nucleotide excision repair is a vital response to DNA damage, including damage from tobacco exposure. Single nucleotide polymorphisms (SNP) in the nucleotide excision repair pathway may encode alterations that affect DNA repair function and therefore influence the risk of pancreatic cancer development. METHODS: A clinic-based case-control study in non-Hispanic white persons compared 1,143 patients with pancreatic adenocarcinoma with 1,097 healthy controls. Twenty-seven genes directly and indirectly involved in the nucleotide excision repair pathway were identified and 236 tag-SNPs were selected from 26 of these (one had no SNPs identified). Association studies were done at the gene level by principal components analysis, whereas recursive partitioning analysis was utilized to identify potential gene-gene and gene-environment interactions within the pathway. At the individual SNP level, adjusted additive, dominant, and recessive models were investigated, and gene-environment interactions were also assessed. RESULTS: Gene level analyses showed an association of the MMS19L genotype (chromosome 10q24.1) with altered pancreatic cancer risk (P = 0.023). Haplotype analysis of MMS19L also showed a significant association (P = 0.0132). Analyses of seven individual SNPs in this gene showed both protective and risk associations for minor alleles, broadly distributed across patient subgroups defined by smoking status, sex, and age. CONCLUSION: In a candidate pathway SNP association study analysis, common variation in a nucleotide excision repair gene, MMS19L, was associated with the risk of pancreatic cancer. 19318433 53 70 pancreatic cancer Disease D010190 19318433 98 104 MMS19L Gene 64210 19318433 285 302 pancreatic cancer Disease D010190 19318433 429 443 adenocarcinoma Disease D000230 19318433 1092 1098 MMS19L Gene 64210 19318433 1142 1159 pancreatic cancer Disease D010190 19318433 1200 1206 MMS19L Gene 64210 19318433 1426 1440 smoking status Environment 64210-D010190 19318433 1442 1445 sex Environment 64210-D010190 19318433 1451 1454 age Environment 64210-D010190 19318433 1578 1584 MMS19L Gene 64210 19318433 1618 1635 pancreatic cancer Disease D010190 20981556|t|ERCC2 Lys751Gln and Asp312Asn polymorphisms and gastric cancer risk: a meta-analysis. 20981556|t|PURPOSE: Studies investigating the association between excision repair cross-complimentary group 2 (ERCC2) polymorphisms and gastric cancer (GC) risk have reported conflicting results. We performed a meta-analysis of published epidemiological studies to derive a more precise estimation of the relationship. METHODS: Published literature from PubMed, EMBASE, and China National Knowledge Infrastructure was retrieved. Ten studies with 2,141 GC cases and 5,343 controls were selected. RESULTS: No association between ERCC2 Lys751Gln polymorphism and GC susceptibility for all genetic models was found. When stratified by race, we found the Gln/Gln genotype carriers might be at high risk of GC among Asians, but not among Caucasians. Also, the pooled results showed there was a significant difference in genotype distribution between non-gastric cardia cancer cases and controls. For ERCC2 Asp312Asn polymorphism, significantly elevated GC risk was associated with Asn/Asn genotype (AA vs. GG + GA: OR = 1.36, 95%CI = 1.04-1.77, P = 0.02). We also found this genotype was associated with GC susceptibility among Asians and subjects without Helicobacter pylori infection. No publication bias was found in the present study. CONCLUSIONS: This meta-analysis concluded that both ERCC2 Lys751Gln and Asp312Asn polymorphisms might contribute to increased risk of GC among Asians. 20981556 0 5 ERCC2 Gene 2068 20981556 48 62 gastric cancer Disease D013274 20981556 55 98 excision repair cross-complimentary group 2 Gene 2068 20981556 100 105 ERCC2 Gene 2068 20981556 125 139 gastric cancer Disease D013274 20981556 141 143 GC Disease D013274 20981556 441 443 GC Disease D013274 20981556 516 521 ERCC2 Gene 2068 20981556 549 551 GC Disease D013274 20981556 690 692 GC Disease D013274 20981556 699 705 Asians Environment 2068-D013274 20981556 852 858 cancer Disease D009369 20981556 883 888 ERCC2 Gene 2068 20981556 936 938 GC Disease D013274 20981556 1087 1089 GC Disease D013274 20981556 1111 1117 Asians Environment 2068-D013274 20981556 1122 1168 subjects without Helicobacter pylori infection Environment 2068-D013274 20981556 1159 1168 infection Disease D007239 20981556 1274 1279 ERCC2 Gene 2068 20981556 1356 1358 GC Disease D013274 20981556 1365 1371 Asians Environment 2068-D013274 20721616|t|MC1R genotype may modify the effect of sun exposure on melanoma risk in the GEM study. 20721616|t|We investigated whether MC1R genotype modifies the effect of sun exposure on melanoma risk in 1,018 cases with multiple melanomas (MPM) and 1,875 controls with one melanoma (SPM). There was some suggestion that MC1R genotype modified the effect of beach and water activities on MPM risk: ORs were 1.94 (95% CI 1.40-2.70) for any activities for no R variants and 1.39 (95% CI 1.05-1.84) with R variants (R151C, R160W, D294H, and D84E) (p for interaction 0.08). MC1R modification of sun exposure effects appeared most evident for MPM of the head and neck: for early life ambient UV, the OR was 4.23 (95% CI 1.76-10.20) with no R and 1.04 (95% CI 0.40-2.68) with R (p for interaction = 0.01; p for three-way interaction = 0.01). Phenotype modified the effect of sun exposure and MPM in a similar manner. We conclude that MC1R and pigmentary phenotype may modify the effects of sun exposure on melanoma risk on more continuously sun-exposed skin. Possible explanations include that risk may saturate with higher sun sensitivity for melanomas on continuously sun-exposed sites but continue to increase as sun exposure increases with lower sun sensitivity, or that sun-sensitive people adapt their behavior by increasing sun protection when exposed. 20721616 0 4 MC1R Gene 4157 20721616 39 51 sun exposure Environment 4157-D008545 20721616 55 63 melanoma Disease D008545 20721616 24 28 MC1R Gene 4157 20721616 77 85 melanoma Disease D008545 20721616 120 129 melanomas Disease D008545 20721616 164 172 melanoma Disease D008545 20721616 211 215 MC1R Gene 4157 20721616 460 464 MC1R Gene 4157 20721616 481 493 sun exposure Environment 4157-D008545 20721616 558 579 early life ambient UV Environment 4157-D008545 20721616 759 771 sun exposure Environment 4157-D008545 20721616 818 822 MC1R Gene 4157 20721616 874 886 sun exposure Environment 4157-D008545 20721616 890 898 melanoma Disease D008545 20721616 907 941 more continuously sun-exposed skin Environment 4157-D008545 20721616 1028 1037 melanomas Disease D008545 18187392|t|Cigarette smoking, N-acetyltransferase 2 genotypes, and breast cancer risk: pooled analysis and meta-analysis. 18187392|t|Approximately 10 years ago, it was noted that smoking increased risk of breast cancer among women with N-acetyltransferase 2 (NAT2) slow acetylation genotypes. This report was followed by a number of studies to address this question. We pooled data from 10 existing studies and also conducted a meta-analysis of 13 studies published from 1996 to October 2006 that were conducted among women, were published in English, and had adequate information on smoking and NAT2 genotyping. Raw data were requested from authors. Unconditional logistic regression was done for pooled analysis, and random effect models was done for meta-analysis. Study heterogeneity was assessed, and sensitivity tests were done when subgroups were excluded from the analysis. In the pooled analysis, there was a significant interaction between smoking, NAT2 genotype, and risk of breast cancer [pack-years (continuous variable, P(interaction) = 0.03)], with higher pack-years significantly associated with an increased risk of breast cancer among women with NAT2 slow genotypes (pooled analysis relative risk, 1.49; 95% confidence interval, 1.08-2.04). These findings were supported by the meta-analysis including all studies; pack-years were significantly associated with risk among slow acetylators in a dose-dependent fashion (meta-analysis relative risk, 1.44; 95% confidence interval, 1.23-1.68 for > or =20 pack-years versus never smokers), but not among rapid acetylators. Similar relationships were noted for smoking status (ever, never) and duration of smoking. Our results show that cigarette smoking is associated with an increase in breast cancer risk among women with NAT2 slow acetylation genotypes. Because slow NAT2 genotypes are present in 50% to 60% of Caucasian populations, smoking is likely to play an important role in breast cancer etiology. 18187392 19 40 N-acetyltransferase 2 Gene 10 18187392 56 69 breast cancer Disease D001943 18187392 72 85 breast cancer Disease D001943 18187392 103 124 N-acetyltransferase 2 Gene 10 18187392 126 130 NAT2 Gene 10 18187392 463 467 NAT2 Gene 10 18187392 817 824 smoking Environment 10-D001943 18187392 826 830 NAT2 Gene 10 18187392 853 866 breast cancer Disease D001943 18187392 931 948 higher pack-years Environment 10-D001943 18187392 1000 1013 breast cancer Disease D001943 18187392 1031 1035 NAT2 Gene 10 18187392 1200 1210 pack-years Environment 10-D001943 18187392 1377 1396 > or =20 pack-years Environment 10-D001943 18187392 1490 1518 smoking status (ever, never) Environment 10-D001943 18187392 1523 1542 duration of smoking Environment 10-D001943 18187392 1566 1583 cigarette smoking Environment 10-D001943 18187392 1618 1631 breast cancer Disease D001943 18187392 1654 1658 NAT2 Gene 10 18187392 1700 1704 NAT2 Gene 10 18187392 1767 1774 smoking Environment 10-D001943 18187392 1814 1827 breast cancer Disease D001943 17460615|t|Gene-by-environment (serotonin transporter and childhood maltreatment) interaction for anxiety sensitivity, an intermediate phenotype for anxiety disorders. 17460615|t|Anxiety sensitivity (AS) is a dispositional characteristic that predisposes to the development of anxiety disorders (eg, panic and post-traumatic stress disorder) and major depression. AS is subject to genetic and environmental influences, the former as yet unidentified and the latter known to include childhood maltreatment. The serotonin transporter gene (SLC6A4) promoter polymorphism (5-HTTLPR) has been associated with depression, but most consistently in the context of environmental stress. We tested the hypothesis that 5-HTTLPR genotype and childhood maltreatment would interact to increase susceptibility to AS in young adults. Subjects were European-American college undergraduates (N=150, median age 18 years) characterized on a measures of AS (Anxiety Sensitivity Index) and retrospective childhood maltreatment (Childhood Trauma Questionnaire [CTQ]). 5-HTTLPR genotypes were obtained from blood-derived DNA. Linear regression was used to model relationships between 5-HTTLPR, childhood emotional abuse, and AS; covariates such as sex, neuroticism, and ancestral proportion scores were incorporated into some models in a larger, ethnically heterogenous sample (N=247) to evaluate robustness of the findings to model assumptions. A statistically signficant interaction was observed between levels of childhood emotional (or physical) maltreatment and 5-HTTLPR genotype. Specifically, S/S individuals with higher levels of maltreatment had significantly higher levels of AS than subjects in other groups. No such relationship was found for neuroticism, attesting to the possible specificity of the findings for AS. Findings were consistently robust to the inclusion of covariates, and were not confounded by population stratification. In conclusion, these results provide evidence of a specific genetic influence on anxiety sensitivity-an intermediate phenotype for anxiety (and depressive) disorders; this effect is modified by severity of childhood maltreatment. These findings are consistent with the notion that 5-HTTLPR operates broadly to moderate emotional responsivity to stress. 17460615 21 42 serotonin transporter Gene 6532 17460615 47 69 childhood maltreatment Environment 6532-D001008 17460615 87 94 anxiety Disease D001008 17460615 138 155 anxiety disorders Disease D001008 17460615 0 7 Anxiety Disease D001008 17460615 98 115 anxiety disorders Disease D001008 17460615 146 161 stress disorder Disease 1 17460615 167 183 major depression Disease D003865 17460615 331 352 serotonin transporter Gene 6532 17460615 359 365 SLC6A4 Gene 6532 17460615 390 398 5-HTTLPR Gene 6532 17460615 425 435 depression Disease D003866 17460615 529 537 5-HTTLPR Gene 6532 17460615 758 765 Anxiety Disease D001008 17460615 837 843 Trauma Disease D014947 17460615 866 874 5-HTTLPR Gene 6532 17460615 981 989 5-HTTLPR Gene 6532 17460615 1050 1061 neuroticism Disease C564323 17460615 1303 1359 levels of childhood emotional (or physical) maltreatment Environment 6532-D001008 17460615 1364 1372 5-HTTLPR Gene 6532 17460615 1418 1447 higher levels of maltreatment Environment 6532-D001008 17460615 1552 1563 neuroticism Disease C564323 17460615 1828 1835 anxiety Disease D001008 17460615 1878 1885 anxiety Disease D001008 17460615 1891 1901 depressive Disease D003866 17460615 1941 1975 severity of childhood maltreatment Environment 6532-D001008 17460615 2028 2036 5-HTTLPR Gene 6532 19252981|t|Genetic variation in genes of the fatty acid synthesis pathway and breast cancer risk. 19252981|t|Fatty acid synthase (FAS) is the major enzyme of lipogenesis. It catalyzes the NADPH-dependent condensation of acetyl-CoA and malonyl-CoA to produce palmitic acid. Transcription of the FAS gene is controlled synergistically by the transcription factors ChREBP (carbohydrate response element-binding protein), which is induced by glucose, and SREBP-1 (sterol response element-binding protein-1), which is stimulated by insulin through the PI3K/Akt signal transduction pathway. We investigated whether the genetic variability of the genes encoding for ChREBP, SREBP and FAS (respectively, MLXIPL, SREBF1 and FASN) is related to breast cancer risk and body-mass index (BMI) by studying 1,294 breast cancer cases and 2,452 controls from the European Prospective Investigation on Cancer (EPIC). We resequenced the FAS gene and combined information of SNPs found by resequencing and SNPs from public databases. Using a tagging approach and selecting 20 SNPs, we covered all the common genetic variation of these genes. In this study we were not able to find any statistically significant association between the SNPs in the FAS, ChREBP and SREPB-1 genes and an increased risk of breast cancer overall and by subgroups of age, menopausal status, hormone replacement therapy (HRT) use or BMI. On the other hand, we found that two SNPs in FASN were associated with BMI. 19252981 67 80 breast cancer Disease D001943 19252981 0 19 Fatty acid synthase Gene 2194 19252981 21 24 FAS Gene 2194 19252981 185 188 FAS Gene 2194 19252981 253 259 ChREBP Gene 51085 19252981 261 306 carbohydrate response element-binding protein Gene 51085 19252981 342 349 SREBP-1 Gene 6720 19252981 351 392 sterol response element-binding protein-1 Gene 6720 19252981 438 442 PI3K Gene 5290 19252981 550 556 ChREBP Gene 51085 19252981 568 571 FAS Gene 2194 19252981 587 593 MLXIPL Gene 51085 19252981 595 601 SREBF1 Gene 6720 19252981 606 610 FASN Gene 2194 19252981 626 639 breast cancer Disease D001943 19252981 689 702 breast cancer Disease D001943 19252981 809 812 FAS Gene 2194 19252981 1118 1121 FAS Gene 2194 19252981 1123 1129 ChREBP Gene 51085 19252981 1173 1186 breast cancer Disease D001943 19252981 1330 1334 FASN Gene 2194 19252981 1356 1359 BMI Environment 2194-D001943 15159300|t|Population-based case-control study of CYP11A gene polymorphism and breast cancer risk. 15159300|t|The CYP11A gene encodes the cholesterol side-chain cleavage enzyme (P450scc) that catalyzes the first and rate-limiting step for the biosynthesis of sex hormones. A pentanucleotide repeat [(TAAAA)n] polymorphism in the 5' of the CYP11A gene has been reported to be related to the risk of polycystic ovary syndrome, an inherited endocrine disorder characterized by hyperandrogenemia. We investigated the association of this polymorphism with breast cancer risk in a population-based case-control study conducted among Chinese women in Shanghai. Genotype assays were completed for 1015 incident breast cancer cases and 1082 community controls. Three common alleles with 4, 6, or 8 TAAAA repeats were identified in the study population. The frequency of the 8 repeat allele was more common in cases (12.6%) than controls (8.5%) (odds ratio = 1.6, 95% confidence interval = 1.3-1.9; P < 0.0001). Compared to subjects who did not carry this allele, adjusted odds ratios were 1.5 (95% confidence interval = 1.2-1.9) and 2.9 (1.3-6.7) (P for trend, <0.001), respectively, for those who carried one and two copies of this allele. This positive association was observed in both pre- and postmenopausal women and all strata defined by major breast cancer risk factors, including years of menstruation, body mass index, and waist-to-hip ratio. The results from this study indicate that the TAAAA repeat polymorphism near the promoter region of the CYP11A gene may be an important susceptibility factor for breast cancer risk. 15159300 39 45 CYP11A Gene 1583 15159300 68 81 breast cancer Disease D001943 15159300 4 10 CYP11A Gene 1583 15159300 229 235 CYP11A Gene 1583 15159300 288 313 polycystic ovary syndrome Disease D011085 15159300 328 346 endocrine disorder Disease D004700 15159300 364 381 hyperandrogenemia Disease D011085 15159300 441 454 breast cancer Disease D001943 15159300 593 606 breast cancer Disease D001943 15159300 1231 1244 breast cancer Disease D001943 15159300 1269 1290 years of menstruation Environment 1583-D001943 15159300 1292 1307 body mass index Environment 1583-D001943 15159300 1313 1331 waist-to-hip ratio Environment 1583-D001943 15159300 1437 1443 CYP11A Gene 1583 15159300 1495 1508 breast cancer Disease D001943 16287156|t|Genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 are associated with susceptibility to lung cancer. 16287156|t|The tumor suppressor TP53 pathway plays a crucial role in preventing carcinogenesis through its ability to impose cell cycle arrest and apoptosis following DNA damage and oncogene activation. MDM2 is a key negative regulator of the TP53 pathway and is overexpressed in many cancers as oncoprotein. We investigated the association between genetic variation in the promoter region of MDM2 (c.-5+309G>T, rs2279744:g.G>T) and the coding region of TP53 (c.215G>C, rs1042522:g.G>C, designated Arg72Pro) and the risk of developing lung cancer. The genotypes of 1,106 patients and 1,420 controls were determined by tetra-primer amplification refractory mutation system (ARMS)-PCR or PCR-based restriction fragment length polymorphism (RFLP). Associations with risk of lung cancer were estimated by logistic regression. We observed an increased lung cancer risk associated with the MDM2 GG (odds ratio [OR] = 1.83, 95% confidence interval [CI] = 1.45-2.32) and TG (OR = 1.33, 95% CI = 1.09-1.63) genotypes. An increased risk was also associated with the TP53 Pro/Pro genotype (OR = 1.47, 95% CI = 1.17-1.85, P = 0.003) compared to the Arg/Arg genotype. The gene-gene interaction of MDM2 and TP53 polymorphisms increased lung cancer risk in a supermultiplicative manner (OR for the presence of both MDM2 GG and TP53 Pro/Pro genotypes = 4.56, 95% CI = 2.76-7.54). Significant interactions were observed between these polymorphisms (respectively and jointly) and smoking (OR = 10.41, 95% CI = 5.26-20.58) for smokers with both the MDM2 GG and TP53 Pro/Pro genotypes. In conclusion, genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 contribute to the risk of developing lung cancer. 16287156 53 57 MDM2 Gene 4193 16287156 62 66 TP53 Gene 7157 16287156 105 116 lung cancer Disease D008175 16287156 4 9 tumor Disease D009369 16287156 21 25 TP53 Gene 7157 16287156 69 83 carcinogenesis Disease D063646 16287156 192 196 MDM2 Gene 4193 16287156 232 236 TP53 Gene 7157 16287156 274 281 cancers Disease D009369 16287156 382 386 MDM2 Gene 4193 16287156 443 447 TP53 Gene 7157 16287156 524 535 lung cancer Disease D008175 16287156 760 771 lung cancer Disease D008175 16287156 836 847 lung cancer Disease D008175 16287156 873 877 MDM2 Gene 4193 16287156 1045 1049 TP53 Gene 7157 16287156 1173 1177 MDM2 Gene 4193 16287156 1182 1186 TP53 Gene 7157 16287156 1211 1222 lung cancer Disease D008175 16287156 1289 1293 MDM2 Gene 4193 16287156 1301 1305 TP53 Gene 7157 16287156 1451 1458 smoking Environment 4193-D008175 16287156 1451 1458 smoking Environment 7157-D008175 16287156 1497 1504 smokers Environment 4193-D008175 16287156 1497 1504 smokers Environment 7157-D008175 16287156 1519 1523 MDM2 Gene 4193 16287156 1531 1535 TP53 Gene 7157 16287156 1623 1627 MDM2 Gene 4193 16287156 1632 1636 TP53 Gene 7157 16287156 1674 1685 lung cancer Disease D008175 18326615|t|Cruciferous vegetables, the GSTP1 Ile105Val genetic polymorphism, and breast cancer risk. 18326615|t|BACKGROUND: Cruciferous vegetables are the primary source of isothiocyanates and other glucosinolate derivatives that are known to induce phase II detoxifying enzymes, including glutathione S-transferases (GSTs). OBJECTIVE: We investigated the independent and combined effects of cruciferous vegetable intake and the GSTP1 Ile(105)Val genetic polymorphism on breast cancer risk. DESIGN: Analyses included 3035 cases and 3037 population controls who were participating in the Shanghai Breast Cancer Study and for whom diet and genetic data were complete (87% of cases and 85% of controls). RESULTS: With the use of multivariate logistic regression, the GSTP1 Val/Val genotype was significantly associated with greater breast cancer risk (OR = 1.50; 95% CI: 1.12, 1.99). The association was significantly greater in premenopausal women (OR = 1.69; 95% CI: 1.17, 2.43) than in postmenopausal women (OR = 1.20; 95% CI: 0.74, 1.92). Total cruciferous vegetable intake was not significantly associated with breast cancer risk, although subjects reporting greater turnip (P for trend < 0.001) and Chinese cabbage (P for trend = 0.049) intakes had a significantly lower postmenopausal breast cancer risk. Women with the GSTP1 Val/Val genotype and low cruciferous vegetable intake had a breast cancer risk 1.74-fold (95% CI: 1.13, 2.67) that of women with the Ile/Ile or Ile/Val genotype. This effect of low cruciferous vegetable intake and the Val/Val genotype was seen predominantly among premenopausal women (OR = 2.08; 95% CI = 1.20, 3.59). CONCLUSIONS: Cruciferous vegetable intake consistent with high isothiocyanate exposure may reduce breast cancer risk. Cruciferous vegetable intake also may ameliorate the effects of the GSTP1 genotype. 18326615 28 33 GSTP1 Gene 2950 18326615 70 83 breast cancer Disease D001943 18326615 317 322 GSTP1 Gene 2950 18326615 359 372 breast cancer Disease D001943 18326615 652 657 GSTP1 Gene 2950 18326615 717 730 breast cancer Disease D001943 18326615 814 833 premenopausal women Environment 2950-D001943 18326615 1001 1014 breast cancer Disease D001943 18326615 1049 1063 greater turnip Environment 2950-D001943 18326615 1090 1105 Chinese cabbage Environment 2950-D001943 18326615 1177 1190 breast cancer Disease D001943 18326615 1212 1217 GSTP1 Gene 2950 18326615 1239 1271 low cruciferous vegetable intake Environment 2950-D001943 18326615 1278 1291 breast cancer Disease D001943 18326615 1395 1427 low cruciferous vegetable intake Environment 2950-D001943 18326615 1634 1647 breast cancer Disease D001943 18326615 1722 1727 GSTP1 Gene 2950 19698717|t|Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhance esophageal cancer risk. 19698717|t|BACKGROUND & AIMS: Esophageal squamous cell carcinoma (ESCC) is prevalent among Asian populations, with marked regional variations in incidence and mortality. Patients with ESCC have a very poor prognosis, but detection of ESCC at earlier stages could improve clinical outcome. Therefore, identification of epidemiologic factors that influence the development of ESCC would facilitate prevention and/or early detection of the disease. METHODS: We performed a 2-step genome-wide association study with subsequent replication analysis using a total of 1070 Japanese ESCC cases and 2836 controls. We also used logistic regression analysis to estimate the effect of gene-gene and gene-environmental interactions. RESULTS: We identified the significant associations of ESCC with 4q21-23 and 12q24 regions, which include nonsynonymous single nucleotide polymorphisms (SNP) in ADH1B (rs1229984, P = 6.76 x 10(-35)) and ALDH2 (rs671, P = 3.68 x 10(-68)) that were previously shown to be associated with ESCC susceptibility. Multiple logistic regression analysis revealed SNP rs671, rs1229984, alcohol drinking, and smoking as the independent risk factors for ESCC (odds ratios of 1.66, 1.85, 1.92, and 1.79, respectively). Moreover, individuals who had both genetic and lifestyle-related risk factors had a nearly 190 times higher risk of ESCC than those who had neither of these. CONCLUSIONS: We found 2 known functional variants involved in the metabolism of alcohol and tobacco by-products as the most significant risk factors for the development of ESCC in a Japanese population. The individuals carrying both risk genotypes have a higher baseline risk of ESCC that is substantially increased by 2 lifestyle risk factors. 19698717 23 28 ADH1B Gene 125 19698717 33 38 ALDH2 Gene 217 19698717 52 59 alcohol Environment 217-D004938 19698717 52 59 alcohol Environment 125-D004938 19698717 64 71 smoking Environment 217-D004938 19698717 64 71 smoking Environment 125-D004938 19698717 96 113 esophageal cancer Disease D004938 19698717 19 53 Esophageal squamous cell carcinoma Disease C562729 19698717 55 59 ESCC Disease C562729 19698717 173 177 ESCC Disease C562729 19698717 223 227 ESCC Disease C562729 19698717 363 367 ESCC Disease C562729 19698717 564 568 ESCC Disease C562729 19698717 764 768 ESCC Disease C562729 19698717 870 875 ADH1B Gene 125 19698717 912 917 ALDH2 Gene 217 19698717 995 999 ESCC Disease C562729 19698717 1085 1101 alcohol drinking Environment 217-D004938 19698717 1085 1101 alcohol drinking Environment 125-D004938 19698717 1107 1114 smoking Environment 217-D004938 19698717 1107 1114 smoking Environment 125-D004938 19698717 1151 1155 ESCC Disease C562729 19698717 1331 1335 ESCC Disease C562729 19698717 1435 1472 the metabolism of alcohol and tobacco Environment 217-D004938 19698717 1435 1472 the metabolism of alcohol and tobacco Environment 125-D004938 19698717 1545 1549 ESCC Disease C562729 19698717 1652 1656 ESCC Disease C562729 20124488|t|Increased risk of colon cancer associated with a genetic polymorphism of SMAD7. 20124488|t|Genome-wide association studies (GWAS) have identified SMAD7 on 8q21 as being associated with colorectal cancer. We evaluated single nucleotide polymorphisms (SNP) in the SMAD7 gene, including rs4939827, rs12953717, and rs4464148, previously identified from GWAS in a large population-based case-control study of colon cancer. We observed that rs12953717 was associated with a statistically significant increased risk of colon cancer [odds ratio, 1.38; 95% confidence intervals (CI), 1.13-1.68; P linear trend < 0.01] for the TT genotype compared with the CC genotype, whereas the CC genotype of the rs4939827 SNP was inversely associated with colon cancer (0.77; 95% CI, 0.64-0.93) relative to the TT genotype. There were no significant differences in association for either of these polymorphisms when stratified by age, tumor site, sex, or family history. The odds ratios between SMAD7 and colon cancer among individuals reporting recent aspirin/nonsteroidal anti-inflammatory drug use was 0.60 (95% CI, 0.43-0.85) for the CC genotype of the rs4939827 polymorphism and 1.69 (95% CI, 1.20-2.38) for the TT genotype of the rs1295371 polymorphism. This result compares to odds ratios of 0.86 (95% CI, 0.68-1.09) for rs4939827 and 1.22 (95% CI, 0.96-1.56) among individuals who did not use aspirin/nonsteroidal anti-inflammatory drugs. An assessment of SMAD7 genotypes with tumor markers did not reveal any significant differences by KRAS2, TP53, CpG island methylator phenotype, or microsatellite instability status. No significant associations were observed for the rs4464148 SNP or other SNPs evaluated in the SMAD7. These results corroborate the findings of GWAS in colon cancer pointing to SMAD7 and reinforce interest in SNPs in this gene. 20124488 18 30 colon cancer Disease D003110 20124488 73 78 SMAD7 Gene 4092 20124488 55 60 SMAD7 Gene 4092 20124488 94 111 colorectal cancer Disease D015179 20124488 171 176 SMAD7 Gene 4092 20124488 313 325 colon cancer Disease D003110 20124488 421 433 colon cancer Disease D003110 20124488 644 656 colon cancer Disease D003110 20124488 823 828 tumor Disease D009369 20124488 883 888 SMAD7 Gene 4092 20124488 893 905 colon cancer Disease D003110 20124488 934 988 recent aspirin/nonsteroidal anti-inflammatory drug use Environment 4092-D003110 20124488 1352 1357 SMAD7 Gene 4092 20124488 1373 1378 tumor Disease D009369 20124488 1433 1438 KRAS2 Gene 3845 20124488 1440 1444 TP53 Gene 7157 20124488 1482 1508 microsatellite instability Disease D053842 20124488 1612 1617 SMAD7 Gene 4092 20124488 1669 1681 colon cancer Disease D003110 20124488 1694 1699 SMAD7 Gene 4092 16112301|t|NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta-analyses. 16112301|t|BACKGROUND: Many reported associations between common genetic polymorphisms and complex diseases have not been confirmed in subsequent studies. An exception could be the association between NAT2 slow acetylation, GSTM1 null genotype, and bladder-cancer risk. However, current evidence is based on meta-analyses of relatively small studies (range 23-374 cases) with some evidence of publication bias and study heterogeneity. Associations between polymorphisms in other NAT and GST genes and bladder-cancer risk have been inconsistent. METHODS: We investigated polymorphisms in NAT2, GSTM1, NAT1, GSTT1, GSTM3, and GSTP1 in 1150 patients with transitional-cell carcinoma of the urinary bladder and 1149 controls in Spain; all the participants were white. We also carried out meta-analyses of NAT2, GSTM1, and bladder cancer that included more than twice as many cases as in previous reports. FINDINGS: In our study, the odds ratios for bladder cancer for individuals with deletion of one or two copies of the GSTM1 gene were 1.2 (95% CI 0.8-1.7) and 1.9 (1.4-2.7) respectively (p for trend <0.0001). Compared with NAT2 rapid or intermediate acetylators, NAT2 slow acetylators had an increased overall risk of bladder cancer (1.4 [1.2-1.7]) that was stronger for cigarette smokers than for never smokers (p for interaction 0.008). No significant associations were found with the other polymorphisms. Meta-analyses showed that the overall association for NAT2 was robust (p<0.0001), and case-only meta-analyses provided support for an interaction between NAT2 and smoking (p for interaction 0.009). The overall association for GSTM1 was also robust (p<0.0001) and was not modified by smoking status (p=0.86). INTERPRETATION: The GSTM1 null genotype increases the overall risk of bladder cancer, and the NAT2 slow-acetylator genotype increases risk particularly among cigarette smokers. These findings provide compelling evidence for the role of common polymorphisms in the aetiology of cancer. RELEVANCE TO PRACTICE: Although the relative risks are modest, these polymorphisms could account for up to 31% of bladder cancers because of their high prevalence. 16112301 0 4 NAT2 Gene 10 16112301 23 28 GSTM1 Gene 2944 16112301 56 70 bladder cancer Disease D001749 16112301 190 194 NAT2 Gene 10 16112301 213 218 GSTM1 Gene 2944 16112301 246 252 cancer Disease D009369 16112301 468 471 NAT Gene 6046 16112301 498 504 cancer Disease D009369 16112301 576 580 NAT2 Gene 10 16112301 582 587 GSTM1 Gene 2944 16112301 589 593 NAT1 Gene 9 16112301 595 600 GSTT1 Gene 2952 16112301 602 607 GSTM3 Gene 2947 16112301 613 618 GSTP1 Gene 2950 16112301 659 691 carcinoma of the urinary bladder Disease 1 16112301 790 794 NAT2 Gene 10 16112301 796 801 GSTM1 Gene 2944 16112301 807 821 bladder cancer Disease D001749 16112301 934 948 bladder cancer Disease D001749 16112301 1007 1012 GSTM1 Gene 2944 16112301 1112 1116 NAT2 Gene 10 16112301 1152 1156 NAT2 Gene 10 16112301 1207 1221 bladder cancer Disease D001749 16112301 1260 1277 cigarette smokers Environment 10-D001749 16112301 1451 1455 NAT2 Gene 10 16112301 1551 1555 NAT2 Gene 10 16112301 1560 1567 smoking Environment 10-D001749 16112301 1623 1628 GSTM1 Gene 2944 16112301 1725 1730 GSTM1 Gene 2944 16112301 1775 1789 bladder cancer Disease D001749 16112301 1799 1803 NAT2 Gene 10 16112301 1863 1880 cigarette smokers Environment 10-D001749 16112301 1982 1988 cancer Disease D009369 16112301 2104 2119 bladder cancers Disease D001749 19492228|t|Cigarette smoking, MDM2 SNP309, gene-environment interactions, and lung cancer risk: a meta-analysis. 19492228|t|MDM2 SNP309 polymorphism was found to contribute to genetic susceptibility to lung cancer in humans. However, association studies on these polymorphisms in lung cancer cases have shown conflicting results. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratio (OR) with 95% confidence interval (CI) was applied to assess the strength of association between MDM2 SNP309 polymorphism and risk of lung cancer development. The logistic regression indicated that the genetic model was most likely to be recessive. Using a recessive model, the pooled OR estimating the genotype GG against the T-allele carriers (GT + TT) were calculated. Eight studies, including 6063 cases and 6678 controls, were involved in this meta-analysis. Overall meta-analysis indicated that MDM2 SNP309 GG genotypes have an approximate 16% increased risk for lung cancer development with a statistical significance (OR = 1.16; 95% CI: 1.01-1.34). In the subgroup analyses based on ethnicities, no significant elevated risk was associated with MDM2 SNP309 genotypes found in Asian and Europeans. No significant increased risk was associated with MDM2 SNP309 genotypes found in ever smokers. MDM2 SNP309 GG genotype had an approximate 36% enhanced risk of lung cancer development with statistical significance in never smokers (OR = 1.36; 95% CI: 1.10-1.68). Although some bias cannot be excluded, this meta-analysis supports the view that MDM2 SNP309 gene is a low-penetrance susceptible gene in the development of lung cancer, and the relationship of MDM2 SNP309 and lung cancer is stronger for never smokers. 19492228 19 23 MDM2 Gene 4193 19492228 67 78 lung cancer Disease D008175 19492228 0 4 MDM2 Gene 4193 19492228 52 74 genetic susceptibility Disease D020022 19492228 78 89 lung cancer Disease D008175 19492228 156 167 lung cancer Disease D008175 19492228 411 415 MDM2 Gene 4193 19492228 448 459 lung cancer Disease D008175 19492228 815 819 MDM2 Gene 4193 19492228 883 894 lung cancer Disease D008175 19492228 1067 1071 MDM2 Gene 4193 19492228 1169 1173 MDM2 Gene 4193 19492228 1214 1218 MDM2 Gene 4193 19492228 1278 1289 lung cancer Disease D008175 19492228 1335 1348 never smokers Environment 4193-D008175 19492228 1462 1466 MDM2 Gene 4193 19492228 1538 1549 lung cancer Disease D008175 19492228 1575 1579 MDM2 Gene 4193 19492228 1591 1602 lung cancer Disease D008175 19492228 1619 1632 never smokers Environment 4193-D008175 19846566|t|Meta- and pooled analyses of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and colorectal cancer: a HuGE-GSEC review. 19846566|t|Worldwide, over 1 million cases of colorectal cancer (CRC) were reported in 2002, with a 50% mortality rate, making CRC the second most common cancer in adults. Certain racial/ethnic populations continue to experience a disproportionate burden of CRC. A common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been associated with a lower risk of CRC. The authors performed both a meta-analysis (29 studies; 11,936 cases, 18,714 controls) and a pooled analysis (14 studies; 5,068 cases, 7,876 controls) of the C677T MTHFR polymorphism and CRC, with stratification by racial/ethnic population and behavioral risk factors. There were few studies on different racial/ethnic populations. The overall meta-analysis odds ratio for CRC for persons with the TT genotype was 0.83 (95% confidence interval (CI): 0.77, 0.90). An inverse association was observed in whites (odds ratio = 0.83, 95% CI: 0.74, 0.94) and Asians (odds ratio = 0.80, 95% CI: 0.67, 0.96) but not in Latinos or blacks. Similar results were observed for Asians, Latinos, and blacks in the pooled analysis. The inverse association between the MTHFR 677TT polymorphism and CRC was not significantly modified by smoking status or body mass index; however, it was present in regular alcohol users only. The MTHFR 677TT polymorphism seems to be associated with a reduced risk of CRC, but this may not hold true for all populations. 19846566 33 68 methylenetetrahydrofolate reductase Gene 4524 19846566 70 75 MTHFR Gene 4524 19846566 100 117 colorectal cancer Disease D015179 19846566 35 52 colorectal cancer Disease D015179 19846566 54 57 CRC Disease D015179 19846566 116 119 CRC Disease D015179 19846566 143 149 cancer Disease D009369 19846566 247 250 CRC Disease D015179 19846566 281 321 5,10-methylenetetrahydrofolate reductase Gene 4524 19846566 323 328 MTHFR Gene 4524 19846566 376 379 CRC Disease D015179 19846566 545 550 MTHFR Gene 4524 19846566 568 571 CRC Disease D015179 19846566 754 757 CRC Disease D015179 19846566 1133 1138 MTHFR Gene 4524 19846566 1162 1165 CRC Disease D015179 19846566 1262 1283 regular alcohol users Environment 4524-D015179 19846566 1294 1299 MTHFR Gene 4524 19846566 1365 1368 CRC Disease D015179 18398040|t|Transcription factor 7-like 2 polymorphism and colon cancer. 18398040|t|Polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene have been associated with insulin sensitivity and diabetes, and the TCF7L2 gene is involved in the Wnt/beta-catenin signaling pathway, all factors thought to be important in the etiology of colon cancer. In this confirmatory study, we evaluated the rs7903146 TCF7L2 polymorphism with colon cancer using previously collected data on 1,578 cases and 1,966 controls. We did not observe a statistically significant association between the rs7903146 polymorphisms and risk of colon cancer [odds ratio (OR), 1.12; 95% confidence interval (95% CI), 0.98-1.28] when evaluating the total population. We did, however, observe a statistically significant interaction between the rs7903146 TCF7L2 polymorphism and recent use of aspirin/nonsteroidal anti-inflammatory drugs (NSAID; P = 0.001). Increased colon cancer risk associated with the T allele was restricted to those without recent use of aspirin/NSAIDs (OR, 1.65; 95% CI, 1.35-2.02, relative to recent aspirin users, i.e., use of aspirin/NSAIDS within the 2 years before diagnosis, with the CC genotype). Among individuals who reported recent use of aspirin/NSAIDs, the T allele reduced risk of colon cancer (OR, 0.78; 95% CI, 0.62-0.98) in a dose-response fashion (P for linear trend across genotypes = 0.03). These data suggest that colon cancer risk associated with the rs7903146 TCF7L2 polymorphism is modified by use of aspirin/NSAIDs. 18398040 0 29 Transcription factor 7-like 2 Gene 6934 18398040 47 59 colon cancer Disease D003110 18398040 21 50 transcription factor 7-like 2 Gene 6934 18398040 52 58 TCF7L2 Gene 6934 18398040 91 110 insulin sensitivity Disease D007333 18398040 115 123 diabetes Disease D003920 18398040 133 139 TCF7L2 Gene 6934 18398040 168 180 beta-catenin Gene 1499 18398040 255 267 colon cancer Disease D003110 18398040 324 330 TCF7L2 Gene 6934 18398040 349 361 colon cancer Disease D003110 18398040 536 548 colon cancer Disease D003110 18398040 743 749 TCF7L2 Gene 6934 18398040 856 868 colon cancer Disease D003110 18398040 921 963 those without recent use of aspirin/NSAIDs Environment 6934-D003110 18398040 1006 1026 recent aspirin users Environment 6934-D003110 18398040 1034 1091 use of aspirin/NSAIDS within the 2 years before diagnosis Environment 6934-D003110 18398040 1147 1175 recent use of aspirin/NSAIDs Environment 6943-D003110 18398040 1206 1218 colon cancer Disease D003110 18398040 1346 1358 colon cancer Disease D003110 18398040 1394 1400 TCF7L2 Gene 6934 18398040 1429 1450 use of aspirin/NSAIDs Environment 6943-D003110 20972438|t|A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci. 20972438|t|We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 x 10(-)(1)(2)) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 x 10(-)(1)(1)) on 19q12 maps to CCNE1 and rs11892031 (P = 1 x 10(-)(7)) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 x 10(-)(1)(1)) and a tag SNP for NAT2 acetylation status (P = 4 x 10(-)(1)(1)), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis. 20972438 47 61 bladder cancer Disease D001749 20972438 61 75 bladder cancer Disease D001749 20972438 379 393 bladder cancer Disease D001749 20972438 568 573 CCNE1 Gene 898 20972438 620 625 UGT1A Gene 7361 20972438 809 814 GSTM1 Gene 2944 20972438 864 868 NAT2 Gene 10 20972438 939 946 smoking Environment 10-D001749 20972438 939 946 smoking Environment 2944-D001749 20972438 1012 1026 bladder cancer Disease D001749 20972438 1083 1097 carcinogenesis Disease D063646 17304047|t|Myeloperoxidase G-463A polymorphism and lung cancer: a HuGE genetic susceptibility to environmental carcinogens pooled analysis. 17304047|t|Myeloperoxidase is a phase I metabolic enzyme that converts the metabolites of benzo[a]pyrene from tobacco smoke into highly reactive epoxides. A polymorphism in the promoter region of myeloperoxidase (463G-->A) has been found to be inversely associated with lung cancer; differences in the association with age and gender have been suggested. We conducted a pooled analysis of individual data from 10 studies (3688 cases and 3874 controls) from the Genetic Susceptibility to Environmental Carcinogens database. The odds ratio for lung cancer was 0.88 (95% confidence interval: 0.80-0.97) for the AG variant of myeloperoxidase G-463A polymorphism, and 0.71 (95% confidence interval: 0.57-0.88) for the AA variant after adjusting for smoking, age, gender, and ethnicity. The inverse association between lung cancer and myeloperoxidase G-463A polymorphism was equally found in males and females (odds ratio for the AA genotype 0.73 [95% confidence interval: 0.56-0.96] and 0.67 [95% confidence interval: 0.46-0.98], respectively), without differences in the association according to age in the two genders. The myeloperoxidase G-463A polymorphism was significantly protective in "ever" smokers but not in "never" smokers. Myeloperoxidase is a key enzyme in tobacco-induced carcinogenesis. 17304047 0 15 Myeloperoxidase Gene 4353 17304047 40 51 lung cancer Disease D008175 17304047 60 67 genetic Disease 1 17304047 0 15 Myeloperoxidase Gene 4353 17304047 185 200 myeloperoxidase Gene 4353 17304047 259 270 lung cancer Disease D008175 17304047 450 472 Genetic Susceptibility Disease D020022 17304047 531 542 lung cancer Disease D008175 17304047 611 626 myeloperoxidase Gene 4353 17304047 802 813 lung cancer Disease D008175 17304047 818 833 myeloperoxidase Gene 4353 17304047 1109 1124 myeloperoxidase Gene 4353 17304047 1177 1191 "ever" smokers Environment 4353-D008175 17304047 1220 1235 Myeloperoxidase Gene 4353 17304047 1271 1285 carcinogenesis Disease D063646 16965239|t|Vitamin D receptor gene polymorphisms, dietary promotion of insulin resistance, and colon and rectal cancer. 16965239|t|Modifiable risk factors in colorectal cancer etiology and their interactions with genetic susceptibility are of particular interest. Functional vitamin D receptor (VDR) gene polymorphisms may influence carcinogenesis through modification of cell growth, protection from oxidative stress, cell-cell matrix effects, or insulin and insulin-like growth factor pathways. We investigated interactions between foods (dairy products, red and processed meat, and whole and refined grains) and dietary patterns (sucrose-to-fiber ratio and glycemic index) associated with insulin resistance with the FokI polymorphism of the VDR gene and colon and rectal cancer risk. Data (diet, anthropometrics, and lifestyle) and DNA came from case-control studies of colon (1,698 cases and 1,861 controls) and rectal cancer (752 cases and 960 controls) in northern California, Utah, and the Twin Cities metropolitan area, Minnesota (colon cancer study only). Unconditional logistic regression models were adjusted for smoking, race, sex, age, body mass index, physical activity, energy intake, dietary fiber, and calcium. The lowest colon cancer risk was observed with the Ff/ff FokI genotypes and a low sucrose-to-fiber ratio. Rectal cancer risk decreased with greater consumption of dairy products and increased with red or processed meat consumption and the FF genotype. Modifiable dietary risk factors may be differentially important among individuals by VDR genotype and may act through the insulin pathway to affect colon cancer risk and through fat, calcium, or other means to influence rectal cancer risk. 16965239 0 18 Vitamin D receptor Gene 7421 16965239 60 67 insulin Gene 3630 16965239 94 107 rectal cancer Disease D012004 16965239 27 44 colorectal cancer Disease D015179 16965239 82 104 genetic susceptibility Disease D020022 16965239 144 162 vitamin D receptor Gene 7421 16965239 164 167 VDR Gene 7421 16965239 202 216 carcinogenesis Disease D063646 16965239 317 324 insulin Gene 3630 16965239 329 336 insulin Gene 3630 16965239 561 568 insulin Gene 3630 16965239 614 617 VDR Gene 7421 16965239 644 650 cancer Disease D009369 16965239 793 799 cancer Disease D009369 16965239 909 921 colon cancer Disease D003110 16965239 1109 1121 colon cancer Disease D003110 16965239 1174 1202 a low sucrose-to-fiber ratio Environment 7421-D003110 16965239 1211 1217 cancer Disease D009369 16965239 1238 1275 greater consumption of dairy products Environment 7421-D012004 16965239 1295 1328 red or processed meat consumption Environment 7421-D012004 16965239 1350 1381 Modifiable dietary risk factors Environment 7421-D012004 16965239 1350 1381 Modifiable dietary risk factors Environment 7421-D003110 16965239 1435 1438 VDR Gene 7421 16965239 1472 1479 insulin Gene 3630 16965239 1498 1510 colon cancer Disease D003110 16965239 1528 1531 fat Environment 7421-D012004 16965239 1533 1540 calcium Environment 7421-D012004 16965239 1577 1583 cancer Disease D009369 19223546|t|Xenobiotic metabolizing gene variants, dietary heterocyclic amine intake, and risk of prostate cancer. 19223546|t|We recently reported that heterocyclic amines (HCA) are associated with prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We now use extensive genetic data from this resource to determine if risks associated with dietary HCAs {2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP); 2-amino-3,8-dimethylimidazo[4,5-b]quinoxaline (MeIQx); and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)} from cooked meat are modified by single nucleotide polymorphisms (SNP) in genes involved in HCA metabolism (CYP1A1, CYP1A2, CYP1B1, GSTA1, GSTM1, GSTM3, GSTP1, NAT1, NAT2, SULT1A1, SULT1A2, and UGT1A locus). We conducted a nested case-control study that included 1,126 prostate cancer cases and 1,127 controls selected for a genome-wide association study for prostate cancer. Unconditional logistic regression was used to estimate odds ratios (OR), 95% confidence intervals (95% CI), and P values for the interaction between SNPs, HCA intake, and risk of prostate cancer. The strongest evidence for an interaction was noted between DiMeIQx and MeIQx and the polymorphism rs11102001 downstream of the GSTM3 locus (P(interaction) = 0.001 for both HCAs; statistically significant after correction for multiple testing). Among men carrying the A variant, the risk of prostate cancer associated with high DiMeIQx intake was 2-fold greater than that with low intake (OR, 2.3; 95% CI, 1.2-4.7). The SNP rs11102001, which encodes a nonsynonymous amino acid change P356S in EPS8L3, is a potential candidate modifier of the effect of HCAs on prostate cancer risk. The observed effect provides evidence to support the hypothesis that HCAs may act as promoters of malignant transformation by altering mitogenic signaling. 19223546 86 101 prostate cancer Disease D011471 19223546 72 87 prostate cancer Disease D011471 19223546 116 126 Colorectal Disease D015179 19223546 132 146 Ovarian Cancer Disease D010051 19223546 552 558 CYP1A1 Gene 1543 19223546 560 566 CYP1A2 Gene 1544 19223546 568 574 CYP1B1 Gene 1545 19223546 576 581 GSTA1 Gene 2938 19223546 583 588 GSTM1 Gene 2944 19223546 590 595 GSTM3 Gene 2947 19223546 597 602 GSTP1 Gene 2950 19223546 604 608 NAT1 Gene 9 19223546 610 614 NAT2 Gene 10 19223546 616 623 SULT1A1 Gene 6817 19223546 625 632 SULT1A2 Gene 6799 19223546 638 643 UGT1A Gene 7361 19223546 713 728 prostate cancer Disease D011471 19223546 803 818 prostate cancer Disease D011471 19223546 999 1014 prostate cancer Disease D011471 19223546 1076 1083 DiMeIQx Environment 2947-D011471 19223546 1088 1093 MeIQx Environment 2947-D011471 19223546 1144 1149 GSTM3 Gene 2947 19223546 1184 1193 both HCAs Environment 2947-D011471 19223546 1307 1322 prostate cancer Disease D011471 19223546 1339 1358 high DiMeIQx intake Environment 2947-D011471 19223546 1509 1515 EPS8L3 Gene 79574 19223546 1568 1572 HCAs Environment 2947-D011471 19223546 1576 1591 prostate cancer Disease D011471 10873932|t|Human leukocyte antigen and season of birth in Japanese patients with schizophrenia. 10873932|t|OBJECTIVE: Five Japanese studies, to the authors' knowledge, without exception, have consistently shown an increased frequency of human leukocyte antigen (HLA)-DR1 in patients with schizophrenia. This suggests an association between HLA-DR1 and schizophrenia in the Japanese population. The mechanism of the association is unknown; however, prenatal infections may be involved. The present study explored factors, including winter birth, that might correlate with this mechanism. Age at onset and gender were also studied. METHOD: Factors were compared between Japanese patients with schizophrenia with and in those without HLA-DR1 (N=60 and N=307, respectively). RESULTS: A significantly higher incidence of births in February and March was observed in patients with (31.7%) than those without (15. 6%) HLA-DR1. No association was found between the presence of HLA-DR1 and other variables. CONCLUSIONS: Although this result is preliminary, it may suggest an interaction between HLA and winter birth in the development of schizophrenia in the Japanese population. 10873932 70 83 schizophrenia Disease D012559 10873932 136 163 leukocyte antigen (HLA)-DR1 Gene 3126 10873932 181 194 schizophrenia Disease D012559 10873932 237 240 DR1 Gene 1810 10873932 245 258 schizophrenia Disease D012559 10873932 350 360 infections Disease D007239 10873932 584 597 schizophrenia Disease D012559 10873932 628 631 DR1 Gene 1810 10873932 709 737 births in February and March Environment 3126-D012559 10873932 808 811 DR1 Gene 1810 10873932 866 869 DR1 Gene 1810 10873932 987 999 winter birth Environment 3126-D012559 10873932 1022 1035 schizophrenia Disease D012559 18155777|t|A functional serotonin transporter promoter gene polymorphism increases ADHD symptoms in delinquents: interaction with adverse childhood environment. 18155777|t|Although attention-deficit/hyperactivity disorder (ADHD) is highly heritable, environmental conditions play an important role in its manifestation during childhood development. Here, we report the results of an investigation on the interaction of adverse childhood environment with a functional polymorphism of the serotonin transporter promoter gene (5-HTTLPR) and its impact on ADHD psychopathology in young adult delinquents. Standardized instruments were used to assess childhood and current ADHD and adverse childhood environment in 184 male delinquents. Each subject was genotyped for 5-HTTLPR long (L) and small (S) alleles. Logistic regression analysis revealed independent effects of high childhood environmental adversity and the 5-HTTLPR LL-genotype on self-reported childhood ADHD and on persistent ADHD. In addition, a significant gene by environment interaction was found, indicating that carriers of at least one 5-HTTLPR short allele are more sensitive to childhood environment adversity than carriers of the LL-genotype. The results support prior findings of association between ADHD and 5-HTTLPR LL-genotype and adverse childhood environment, and they underline the need for further investigation of gene by environment interaction with respect to ADHD. 18155777 13 34 serotonin transporter Gene 6532 18155777 72 76 ADHD Disease D001289 18155777 119 148 adverse childhood environment Environment 6532-D001289 18155777 9 49 attention-deficit/hyperactivity disorder Disease D001289 18155777 51 55 ADHD Disease D001289 18155777 315 336 serotonin transporter Gene 6532 18155777 352 360 5-HTTLPR Gene 6532 18155777 380 384 ADHD Disease D001289 18155777 496 500 ADHD Disease D001289 18155777 591 599 5-HTTLPR Gene 6532 18155777 740 748 5-HTTLPR Gene 6532 18155777 788 792 ADHD Disease D001289 18155777 811 815 ADHD Disease D001289 18155777 928 936 5-HTTLPR Gene 6532 18155777 972 1003 childhood environment adversity Environment 6532-D001289 18155777 1096 1100 ADHD Disease D001289 18155777 1105 1113 5-HTTLPR Gene 6532 18155777 1130 1159 adverse childhood environment Environment 6532-D001289 18155777 1266 1270 ADHD Disease D001289 19462450|t|+331G/A variant in the progesterone receptor gene, postmenopausal hormone use and risk of breast cancer. 19462450|t|A functional promoter polymorphism in the progesterone receptor (PR) gene previously has been associated with an increased risk of postmenopausal breast cancer. Whether the relationship between genetic variation in PR and risk of breast cancer is modified by postmenopausal hormone (PMH) use is unknown. Thus, we conducted a case-control study nested within the prospective Nurses' Health Study to evaluate if the risk of breast cancer associated with having the +331 A risk allele was modified by PMH use. Genotyping of this SNP was available for 1,664 postmenopausal breast cancer cases and 2,391 controls. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer. Women who were carriers of 1 or both variant A alleles had a 31% increased risk of developing breast cancer (95% CI 1.04-1.65). PMH use significantly modified the association between the +331G/A polymorphism and risk (p-interaction <0.05). Among never users of PMH, women who were variant carriers had a significantly increased risk of breast cancer compared to those with the wild-type genotype (OR = 2.57; 95% CI 1.64-4.02). The +331G/A polymorphism was not associated with breast cancer risk among past (OR = 1.23; 95% CI 0.77-1.97) or current (OR = 1.14; 95% CI 0.84-1.56) PMH users. The data from this large prospective study provide evidence for a 2-fold increased risk of developing postmenopausal breast cancer among never users of PMH with the +331G/A SNP. This finding adds to the evidence that the PR has an important etiologic role in breast cancer and should be evaluated in future studies. 19462450 23 44 progesterone receptor Gene 5241 19462450 90 103 breast cancer Disease D001943 19462450 42 63 progesterone receptor Gene 5241 19462450 65 67 PR Gene 5241 19462450 146 159 breast cancer Disease D001943 19462450 215 217 PR Gene 5241 19462450 230 243 breast cancer Disease D001943 19462450 422 435 breast cancer Disease D001943 19462450 569 582 breast cancer Disease D001943 19462450 711 724 breast cancer Disease D001943 19462450 820 833 breast cancer Disease D001943 19462450 854 861 PMH use Environment 5241-D001943 19462450 972 990 never users of PMH Environment 5241-D001943 19462450 1062 1075 breast cancer Disease D001943 19462450 1202 1215 breast cancer Disease D001943 19462450 1431 1444 breast cancer Disease D001943 19462450 1451 1469 never users of PMH Environment 5241-D001943 19462450 1535 1537 PR Gene 5241 19462450 1573 1586 breast cancer Disease D001943 18059035|t|Leptin and leptin receptor genotypes and colon cancer: gene-gene and gene-lifestyle interactions. 18059035|t|Leptin may play an important role in colorectal cancer because of its role in energy balance, insulin and inflammation. We evaluated the LEP rs2167270 (19 G > A) and rs7799039 (-2548 G > A) polymorphisms and the leptin receptor, LEPR rs6588147 (located in intron 2), polymorphism with risk of developing colon cancer in a study of 1,567 cases and 1,965 controls. We evaluated the effects of the polymorphisms with body mass index (BMI), recent use of aspirin/NSAIDs and genetic variations in genes related to insulin signaling pathways including insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), and insulin-related substrates 1 and 2 (IRS1, IRS2) and the vitamin D receptor (VDR). We observed a slight reduction in colon cancer risk with the AA LEP rs2167270 genotype (OR 0.79 95% CI 0.64, 0.98) and although not reaching statistical significance, with the combined GG LEP rs2167270 and GG LEPR rs6588147 (OR 0.70, 95% CI 0.49, 1.02) genotypes. BMI did not interact with any of these polymorphisms to alter colon cancer risk. However, recent aspirin/NSAID use significantly interacted with both LEP polymorphisms. Likewise, variants of IGF1 and IRS2 interacted with the LEP rs2167270 polymorphism. VDR polymorphisms interacted with all LEP and LEPR polymorphisms. These data support an association between LEP and colon cancer. They also suggest that the mechanisms linking leptin to colon cancer may be independent of energy balance. 18059035 41 53 colon cancer Disease D003110 18059035 37 54 colorectal cancer Disease D015179 18059035 106 118 inflammation Disease D007249 18059035 137 140 LEP Gene 3952 18059035 229 233 LEPR Gene 3953 18059035 304 316 colon cancer Disease D003110 18059035 546 574 insulin-like growth factor 1 Gene 3479 18059035 576 580 IGF1 Gene 3479 18059035 583 627 insulin-like growth factor binding protein 3 Gene 3486 18059035 629 635 IGFBP3 Gene 3486 18059035 678 682 IRS1 Gene 3667 18059035 684 688 IRS2 Gene 8660 18059035 698 716 vitamin D receptor Gene 7421 18059035 718 721 VDR Gene 7421 18059035 758 770 colon cancer Disease D003110 18059035 788 791 LEP Gene 3952 18059035 912 915 LEP Gene 3952 18059035 933 937 LEPR Gene 3953 18059035 1050 1062 colon cancer Disease D003110 18059035 1078 1102 recent aspirin/NSAID use Environment 3952-D003110 18059035 1138 1141 LEP Gene 3952 18059035 1179 1183 IGF1 Gene 3479 18059035 1188 1192 IRS2 Gene 8660 18059035 1213 1216 LEP Gene 3952 18059035 1241 1244 VDR Gene 7421 18059035 1279 1282 LEP Gene 3952 18059035 1287 1291 LEPR Gene 3953 18059035 1349 1352 LEP Gene 3952 18059035 1357 1369 colon cancer Disease D003110 18059035 1427 1439 colon cancer Disease D003110 22344756|t|Combined effects of E2F1 and E2F2 polymorphisms on risk and early onset of squamous cell carcinoma of the head and neck. 22344756|t|Deregulated expression of most members of the E2F family has been detected in many human cancers. We examined the association of common single nucleotide polymorphisms (SNPs) of E2F transcription factors 1 and 2 (E2F1 and E2F2) with risk of squamous cell carcinoma of the head and neck (SCCHN) in 1,096 SCCHN patients and 1,090 cancer-free controls. We genotyped 10 selected SNPs in E2F1 and E2F2, including those at the near 5'-untranslated region (UTR), microRNA (miRNA)-binding sites at the near 3'-UTR and tagSNPs according to bioinformatics analysis. Although none of the selected SNPs alone was significantly associated with risk of SCCHN, there was a statistically significantly increased risk of SCCHN associated with the combined risk genotypes (i.e., rs3213182 AA, rs3213183 GG, rs3213180 GG, rs321318121 GG, rs2742976 GT+TT, rs6667575 GA+AA, rs3218203 CC, rs3218148 AA, rs3218211 CC, and rs3218123 GT+TT). Compared with those with 0-4 risk genotypes, an increased risk was observed for those who carried 5-8 risk genotypes (adjusted OR = 1.04; 95% CI = 0.86-1.26) and 9-10 risk genotypes (adjusted OR = 1.62; 95% CI = 1.14-2.30) in a dose-response manner (P = 0.045). Furthermore, the joint effect was more pronounced among patients with oropharyngeal cancer, younger adults (C transition in the 3' noncoding region) and CYP1A1*2C (A-->G transition in exon 7, resulting in a substitution of Val for Ile) in 1134 patients with breast carcinoma and 1227 controls. RESULTS: The frequencies of the variant allele were 38.3% and 38.8% among cases and controls (P = 0.91), respectively, for the CYP1A1*2A polymorphism, and 23.1% and 24.8% (P = 0.26) for the CYP1A1*2C polymorphism. Homozygosity for both variant alleles in these 2 polymorphic sites (CYP1A1*2B) was associated with a borderline significant odds ratio (OR) of 0.71 (95% confidence interval [CI], 0.47-1.06). The reduced risk was more pronounced among postmenopausal women with long duration (> 30 yrs) of menstruation (OR = 0.43; 95% CI, 0.19-0.99) or among women with a low waist-to-hip ratio (OR = 0.52; 95% CI, 0.28-0.94). CONCLUSIONS: Results from the current study suggest that homozygosity for the CYP1A1*2A and CYP1A1*2C alleles in the CYP1A1 gene may be associated with a reduced risk for breast carcinoma, particularly among lean women with long-term endogenous estrogen exposure. 15856430 17 23 CYP1A1 Gene 1543 15856430 28 44 breast carcinoma Disease D001943 15856430 12 31 Cytochrome P450 1A1 Gene 1543 15856430 33 39 CYP1A1 Gene 1543 15856430 147 163 breast carcinoma Disease D001943 15856430 224 230 CYP1A1 Gene 1543 15856430 251 267 breast carcinoma Disease D001943 15856430 387 393 CYP1A1 Gene 1543 15856430 400 406 CYP1A1 Gene 1543 15856430 488 494 CYP1A1 Gene 1543 15856430 548 554 CYP1A1 Gene 1543 15856430 653 669 breast carcinoma Disease D001943 15856430 816 822 CYP1A1 Gene 1543 15856430 879 885 CYP1A1 Gene 1543 15856430 971 977 CYP1A1 Gene 1543 15856430 1163 1203 long duration (> 30 yrs) of menstruation Environment 1543-D001943 15856430 1255 1279 a low waist-to-hip ratio Environment 1543-D001943 15856430 1390 1396 CYP1A1 Gene 1543 15856430 1404 1410 CYP1A1 Gene 1543 15856430 1429 1435 CYP1A1 Gene 1543 15856430 1483 1499 breast carcinoma Disease D001943 15856430 1520 1574 lean women with long-term endogenous estrogen exposure Environment 1543-D001943 19796841|t|CYP2E1 Rsa I/Pst I polymorphism is associated with lung cancer risk among Asians. 19796841|t|The genetic polymorphism of CYP2E1 Rsa I/Pst I is thought to have significant effect on lung cancer risk, but the results are inconsistent. In this meta-analysis, we assessed 21 published studies involving 9380 subjects of the association between CYP2E1 Rsa I/Pst I polymorphism and lung cancer risk. For the homozygote c2/c2 and c2 allele carriers (c1/c2+c2/c2), the pooled ORs for all studies were 0.734 (95% CI=0.628-0.847; P=0.035 for heterogeneity) and 0.852 (95% CI=0.777-0.933; P=0.004 for heterogeneity) when compared with the homozygous wild-type genotype (c1/c1). In the stratified analysis by ethnicity, the same significant risks were found among Asians for both the c2 allele carriers and homozygote c2/c2. Among mixed populations, only significant risk was associated with c2 allele carriers. No significant associations were found in all Caucasians genetic models. In the subgroup analyses by pathological types, for lung SC the ORs of the c2 allele carriers and the homozygote c2/c2 were 0.749 (95% CI=0.683-0.813; P=0.247 for heterogeneity) and 0.726 (95% CI=0.662-0.847; P=0.006 for heterogeneity), respectively. In the subgroup analyses by smoking status, there were no significant associations among smokers or non-smokers subgroup. This meta-analysis suggests that CYP2E1 Rsa I/Pst I c2 allele is a decreased risk factor for the developing lung cancer among Asians and lung SC. 19796841 0 6 CYP2E1 Gene 1571 19796841 13 18 Pst I Gene 6690 19796841 51 62 lung cancer Disease D008175 19796841 74 80 Asians Environment 1571-D008175 19796841 28 34 CYP2E1 Gene 1571 19796841 41 46 Pst I Gene 6690 19796841 88 99 lung cancer Disease D008175 19796841 247 253 CYP2E1 Gene 1571 19796841 260 265 Pst I Gene 6690 19796841 283 294 lung cancer Disease D008175 19796841 350 355 c1/c2 Gene 3183 19796841 659 665 Asians Environment 1571-D008175 19796841 932 939 lung SC Environment 1571-D008175 19796841 1286 1292 CYP2E1 Gene 1571 19796841 1299 1304 Pst I Gene 6690 19796841 1361 1372 lung cancer Disease D008175 19796841 1379 1385 Asians Environment 1571-D008175 19796841 1390 1397 lung SC Environment 1571-D008175 18843020|t|Genetic variation in calcium-sensing receptor and risk for colon cancer. 18843020|t|BACKGROUND: Experimental and epidemiologic studies have suggested that high calcium intake is associated with decreased colon cancer risk, yet very limited data are available for candidate genes in the calcium-vitamin D pathway and colon cancer risk. To address this, we evaluated whether calcium-sensing receptor (CASR) single-nucleotide polymorphisms are associated with colon cancer risk. We also examined interactions among CASR, calcium, and vitamin D intake and previously genotyped vitamin D-related genes. METHODS: We conducted a large multicenter population-based case-control study of 1,600 cases and 1,949 controls. Seventeen tagging single-nucleotide polymorphisms for CASR were selected from common single-nucleotide polymorphisms (minor allele frequency, >or=5%) based on resequencing data. Haplotypes were estimated and evaluated using HaploStats. RESULTS: We did not observe an association between any CASR genotypes or haplotypes and colon cancer risk overall. However, when stratified by anatomic site, statistically significant associations were seen with risk for proximal colon cancer [rs10934578 TT: odds ratio, 1.35; 95% confidence interval (95% CI), 1.01-1.81; rs12485716 AG/AA: odds ratio, 0.84; 95% CI, 0.71-1.00; rs4678174 CT/CC: odds ratio, 0.83; 95% CI, 0.70-0.98; rs2270916 CC: odds ratio, 0.43; 95% CI, 0.19-0.97]. Concordantly, we observed a suggested association for a CASR haplotype (rs4678174, rs2270916) with risk for proximal colon cancer (global P=0.08). We did not observe any meaningful gene-environment (calcium and vitamin D) or gene-gene (CYP24A1, CYP27B1, and VDR) interactions with CASR genotypes and colon cancer risk. CONCLUSION: Our study does not provide evidence for an overall association between CASR single-nucleotide polymorphisms and colon cancer; however, results suggest a possible role of CASR on proximal colon cancer, and subsite differences are consistent with known calcium biology. Nonetheless, these findings require confirmation. 18843020 59 71 colon cancer Disease D003110 18843020 120 132 colon cancer Disease D003110 18843020 232 244 colon cancer Disease D003110 18843020 315 319 CASR Gene 846 18843020 373 385 colon cancer Disease D003110 18843020 428 432 CASR Gene 846 18843020 681 685 CASR Gene 846 18843020 918 922 CASR Gene 846 18843020 951 963 colon cancer Disease D003110 18843020 1093 1105 colon cancer Disease D003110 18843020 1402 1406 CASR Gene 846 18843020 1454 1475 proximal colon cancer Environment 846-D003110 18843020 1463 1475 colon cancer Disease D003110 18843020 1582 1589 CYP24A1 Gene 1591 18843020 1591 1598 CYP27B1 Gene 1594 18843020 1604 1607 VDR Gene 7421 18843020 1627 1631 CASR Gene 846 18843020 1646 1658 colon cancer Disease D003110 18843020 1748 1752 CASR Gene 846 18843020 1789 1801 colon cancer Disease D003110 18843020 1847 1851 CASR Gene 846 18843020 1855 1876 proximal colon cancer Environment 846-D003110 18843020 1864 1876 colon cancer Disease D003110 17301695|t|Interaction of soy and 17beta-HSD1 gene polymorphisms in the risk of endometrial cancer. 17301695|t|BACKGROUND: In-vitro studies have found that soy isoflavones can inhibit the activity of 17beta-hydroxysteroid dehydrogenase type I, a key enzyme in catalyzing estrone (E1), to the biologically more active estradiol (E2). OBJECTIVE: We hypothesized that soy food consumption may interact with polymorphisms in the 17beta-HSD1 gene in the development of endometrial cancer and evaluated this hypothesis in the Shanghai Endometrial Cancer Study. METHODS: Shanghai Endometrial Cancer Study is a population-based case-control study conducted among Chinese women in Shanghai. This study consisted of 1204 incident endometrial cancer cases diagnosed between 30 and 69 years of age and 1212 age frequency-matched community controls recruited from 1997 to 2003. Overall participation rates were 82.8% for cases and 74.4% for controls, whereas the DNA collection rates were 95.1% for cases and 94.2% for controls. RESULTS: We found that women carrying at least one A allele of the rs605059 polymorphism had a significant 18% reduction in risk of endometrial cancer compared with those without an A allele, and the association was primarily restricted to premenopausal women. The odds ratio (95% confidence interval) was 0.65 (0.47-0.88) for premenopausal women with at least one A allele versus those without an A allele. We also found that among premenopausal women soy isoflavone intake significantly interacted with the rs605059 genotype in relation to endometrial cancer and that the inverse association between soy isoflavone intake and endometrial cancer only appeared among those with at least one A allele of the rs605059 polymorphism. Among postmenopausal women, the association of soy isoflavone intake with endometrial cancer did not differ by 17beta-HSD1 genotypes. We did not find that the rs2676530 polymorphism was significantly associated with endometrial cancer risk. CONCLUSIONS: Our results suggest that soy consumption may interact with polymorphisms in the 17beta-HSD1 gene in relation to endometrial cancer risk. Further studies are warranted to confirm our results. 17301695 15 18 soy Environment 3292-D016889 17301695 23 34 17beta-HSD1 Gene 26871 17301695 23 34 17beta-HSD1 Gene 3292 17301695 69 87 endometrial cancer Disease D016889 17301695 89 124 17beta-hydroxysteroid dehydrogenase Gene 51478 17301695 314 325 17beta-HSD1 Gene 26871 17301695 314 325 17beta-HSD1 Gene 3292 17301695 353 371 endometrial cancer Disease D016889 17301695 418 436 Endometrial Cancer Disease D016889 17301695 462 480 Endometrial Cancer Disease D016889 17301695 609 627 endometrial cancer Disease D016889 17301695 1037 1055 endometrial cancer Disease D016889 17301695 1358 1379 soy isoflavone intake Environment 3292-D016889 17301695 1447 1465 endometrial cancer Disease D016889 17301695 1507 1528 soy isoflavone intake Environment 3292-D016889 17301695 1533 1551 endometrial cancer Disease D016889 17301695 1709 1727 endometrial cancer Disease D016889 17301695 1746 1757 17beta-HSD1 Gene 26871 17301695 1746 1757 17beta-HSD1 Gene 3292 17301695 1851 1869 endometrial cancer Disease D016889 17301695 1914 1929 soy consumption Environment 3292-D016889 17301695 1969 1980 17beta-HSD1 Gene 26871 17301695 1969 1980 17beta-HSD1 Gene 3292 17301695 2001 2019 endometrial cancer Disease D016889 22678777|t|PTGS1, PTGS2, ALOX5, ALOX12, ALOX15, and FLAP SNPs: interaction with fatty acids in colon cancer and rectal cancer. 22678777|t|Dietary polyunsaturated fatty acids (PUFAs) can be converted to prostaglandins and leukotrienes. Oxygenation of omega-6 PUFAs generally results in the production of pro-inflammatory mediators, whereas oxygenated products of omega-3 (n-3) PUFAs generally have lower inflammatory activity. We hypothesize that elevated n-3 PUFA intakes from fish are associated with lower risk of colorectal cancer among those with genetic variants that result in higher levels of pro-inflammatory mediators. In population-based case-control studies of colon (case n = 1,574) and rectal cancer (case n = 791) and disease-free controls (n = 2,969), we investigated interactions between dietary fatty acid intake and 107 candidate polymorphisms and tagSNPs in PTGS1, PTGS2, ALOX12, ALOX5, ALOX15, and FLAP. The two studies used an identical genotyping protocol. We observed interactions and statistically significant increases in colon cancer risk for low docosahexaenoic acid intake among those with the PTGS1 rs10306110 (-1,053 A > G) variant genotypes (OR = 1.6, 95 % confidence interval = 1.1-2.3, adj. p = 0.06) and rectal cancer risk for low total fat intake among those with the variant PTGS1 rs10306122 (7,135 A > G) (OR(vs.wt) = 1.80, 1.02-2.99; adj. p = 0.08). The ALOX15 rs11568131 (10,339 C > T) wild type in combination with a high inflammation score (low EPA intake, high AA intake, no regular NSAID use, high BMI, smoking) was associated with increased colon cancer risk (OR = 2.28, 1.7-3.07). Rectal cancer risk was inversely associated with a low inflammation score among PTGS2 rs4648276 (3,934 T > C) variant allele carriers (OR = 0.49, 0.25-0.75). Overall, these data provide some modest evidence for interactions between dietary fat intake and genetic variation in genes involved in eicosanoid metabolism and colorectal cancer risk. 22678777 0 5 PTGS1 Gene 5742 22678777 7 12 PTGS2 Gene 5743 22678777 14 19 ALOX5 Gene 240 22678777 21 27 ALOX12 Gene 239 22678777 29 35 ALOX15 Gene 246 22678777 41 45 FLAP Gene 241 22678777 84 96 colon cancer Disease D003110 22678777 101 114 rectal cancer Disease D012004 22678777 321 325 PUFA Gene 9933 22678777 378 395 colorectal cancer Disease D015179 22678777 568 574 cancer Disease D009369 22678777 739 744 PTGS1 Gene 5742 22678777 746 751 PTGS2 Gene 5743 22678777 753 759 ALOX12 Gene 239 22678777 761 766 ALOX5 Gene 240 22678777 768 774 ALOX15 Gene 246 22678777 780 784 FLAP Gene 241 22678777 909 921 colon cancer Disease D003110 22678777 931 962 low docosahexaenoic acid intake Environment 5742-D003110 22678777 984 989 PTGS1 Gene 5742 22678777 1107 1113 cancer Disease D009369 22678777 1123 1143 low total fat intake Environment 5742-D012004 22678777 1173 1178 PTGS1 Gene 5742 22678777 1254 1260 ALOX15 Gene 246 22678777 1317 1342 a high inflammation score Environment 246-D003110 22678777 1324 1336 inflammation Disease D007249 22678777 1344 1358 low EPA intake Environment 246-D003110 22678777 1360 1374 high AA intake Environment 246-D003110 22678777 1376 1396 no regular NSAID use Environment 246-D003110 22678777 1398 1406 high BMI Environment 246-D003110 22678777 1408 1415 smoking Environment 246-D003110 22678777 1447 1459 colon cancer Disease D003110 22678777 1495 1501 cancer Disease D009369 22678777 1537 1561 a low inflammation score Environment 5743-D012004 22678777 1543 1555 inflammation Disease D007249 22678777 1568 1573 PTGS2 Gene 5743 22678777 1808 1825 colorectal cancer Disease D015179 19369581|t|Common genetic variants on 5p15.33 contribute to risk of lung adenocarcinoma in a Chinese population. 19369581|t|Chromosome 5p15.33, containing TERT and CLPTM1L genes, was recently identified as one of the susceptible regions for lung cancer in Caucasian populations. We hypothesized that single-nucleotide polymorphisms (SNPs) identified in this region in Caucasians are also important in the development of lung cancer in Chinese population. To test this hypothesis, we genotyped two most significant SNPs reported in Caucasians, rs2736100A/C and rs402710C/T at 5p15.33, in a case-control study with 1221 non-small cell lung cancer (NSCLC) cases and 1344 cancer-free controls in a Chinese population. We found that rs2736100C allele in TERT gene was associated with a significantly increased risk of NSCLC with adjusted odds ratios of 1.26 [95% confidence interval (CI) = 1.05-1.51] and 1.31 (95% CI = 1.04-1.66) for one or two copies of the variant C allele, respectively. This significant association was more prominent among female (P for heterogeneity: 0.044), non-smokers (P for heterogeneity: 0.054) and/or the subjects with adenocarcinoma (P for heterogeneity: 0.058). However, no significant association was found between rs402710C/T and NSCLC risk. These results suggest that genetic variants in 5p15.33, especially in TERT gene, may also predispose the susceptibility of lung cancer, especially adenocarcinoma, in Chinese population. 19369581 57 76 lung adenocarcinoma Disease C538231 19369581 31 35 TERT Gene 7015 19369581 40 47 CLPTM1L Gene 81037 19369581 117 128 lung cancer Disease D008175 19369581 296 307 lung cancer Disease D008175 19369581 494 520 non-small cell lung cancer Disease D002289 19369581 522 527 NSCLC Disease D002289 19369581 544 550 cancer Disease D009369 19369581 625 629 TERT Gene 7015 19369581 689 694 NSCLC Disease D002289 19369581 917 923 female Environment 7015-D002289 19369581 954 965 non-smokers Environment 7015-D002289 19369581 1020 1034 adenocarcinoma Disease D000230 19369581 1020 1034 adenocarcinoma Environment 7015-D002289 19369581 1135 1140 NSCLC Disease D002289 19369581 1217 1221 TERT Gene 7015 19369581 1270 1281 lung cancer Disease D008175 19369581 1294 1308 adenocarcinoma Disease D000230 19369581 1294 1308 adenocarcinoma Environment 7015-D002289 22405187|t|Breastfeeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. 22405187|t|INTRODUCTION: Breastfeeding has been inversely related to breast cancer risk in the general population. Clarifying the role of breastfeeding among women with a BRCA1 or BRCA2 mutation may be helpful for risk assessment and for recommendations regarding prevention. We present an updated analysis of breastfeeding and risk of breast cancer using a large matched sample of BRCA mutation carriers. METHODS: We conducted a case-control study of 1,665 pairs of women with a deleterious mutation in either BRCA1 (n = 1,243 pairs) or BRCA2 (n = 422 pairs). Breast cancer cases and unaffected controls were matched on year of birth, mutation status, country of residence and parity. Information about reproductive factors, including breastfeeding for each live birth, was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the association between ever having breastfed, as well as total duration of breastfeeding, and the risk of breast cancer. RESULTS: Among BRCA1 mutation carriers, breastfeeding for at least one year was associated with a 32% reduction in risk (OR = 0.68; 95% CI 0.52 to 0.91; P = 0.008); breastfeeding for two or more years conferred a greater reduction in risk (OR = 0.51; 95% CI 0.35 to 0.74). Among BRCA2 mutation carriers, there was no significant association between breastfeeding for at least one year and breast cancer risk (OR = 0.83; 95% CI 0.53 to 1.31; P = 0.43). CONCLUSIONS: These data extend our previous findings that breastfeeding protects against BRCA1-, but not BRCA2-associated breast cancer. BRCA mutation carriers should be advised of the benefit of breastfeeding in terms of reducing breast cancer risk. 22405187 30 43 breast cancer Disease D001943 22405187 47 52 BRCA1 Gene 672 22405187 57 62 BRCA2 Gene 675 22405187 58 71 breast cancer Disease D001943 22405187 160 165 BRCA1 Gene 672 22405187 169 174 BRCA2 Gene 675 22405187 325 338 breast cancer Disease D001943 22405187 371 375 BRCA Gene 672 22405187 500 505 BRCA1 Gene 672 22405187 527 532 BRCA2 Gene 675 22405187 550 563 Breast cancer Disease D001943 22405187 979 992 breast cancer Disease D001943 22405187 1009 1014 BRCA1 Gene 672 22405187 1034 1069 breastfeeding for at least one year Environment 672-D001943 22405187 1159 1194 breastfeeding for two or more years Environment 672-D001943 22405187 1273 1278 BRCA2 Gene 675 22405187 1383 1396 breast cancer Disease D001943 22405187 1504 1517 breastfeeding Environment 672-D001943 22405187 1535 1540 BRCA1 Gene 672 22405187 1551 1556 BRCA2 Gene 675 22405187 1568 1581 breast cancer Disease D001943 22405187 1583 1587 BRCA Gene 672 22405187 1642 1655 breastfeeding Environment 672-D001943 22405187 1677 1690 breast cancer Disease D001943 18648013|t|Common MMP-7 polymorphisms and breast cancer susceptibility: a multistage study of association and functionality. 18648013|t|Matrix metalloproteinase-7 (MMP-7) is a small secreted proteolytic enzyme with broad substrate specificity against ECM and non-ECM components. Known to be vital for tumor invasion and metastasis, accumulating evidence also implicates MMP-7 in cancer development. Using data from the Shanghai Breast Cancer Study, we conducted a two-stage study to evaluate the association of MMP-7 single nucleotide polymorphisms (SNPs) with breast cancer risk. Additionally, associated SNPs were characterized by laboratory assays. In stage 1, 11 SNPs were genotyped among 1,079 incident cases and 1,082 community controls using an Affymetrix Genotyping System. Promising SNPs were selected for stage 2 evaluation and genotyped by TaqMan allelic discrimination assays in an independent set of 1,911 cases and 1,811 controls. Three SNPs were selected for stage 2 validation (rs880197, rs10895304, and rs12184413); one had highly consistent results between the two stages of the study. In combined analysis, homozygosity for the variant T allele for rs12184413 was associated with an odds ratio (OR) of 0.7 [95% confidence interval (95% CI), 0.6-0.9] compared with the common C allele. This effect was slightly more pronounced in postmenopausal women (OR, 0.6; 95% CI, 0.4-0.8) than in premenopausal women (OR, 0.8; 95% CI, 0.6-1.1). This SNP is located 3' of the MMP-7 gene, in an area enriched with CTCF binding sites. In silico analysis suggested a regulatory role for this region, and our in vitro assays showed an allelic difference in nuclear protein binding capacity. Results from our study suggest that common MMP-7 genetic polymorphisms may contribute to breast cancer susceptibility. 18648013 7 12 MMP-7 Gene 4316 18648013 31 44 breast cancer Disease D001943 18648013 0 26 Matrix metalloproteinase-7 Gene 4316 18648013 28 33 MMP-7 Gene 4316 18648013 115 118 ECM Gene 22915 18648013 127 130 ECM Gene 22915 18648013 165 170 tumor Disease D009369 18648013 184 194 metastasis Disease D009362 18648013 234 239 MMP-7 Gene 4316 18648013 243 249 cancer Disease D009369 18648013 375 380 MMP-7 Gene 4316 18648013 425 438 breast cancer Disease D001943 18648013 1212 1232 postmenopausal women Environment 4316-D001943 18648013 1346 1351 MMP-7 Gene 4316 18648013 1383 1387 CTCF Gene 10664 18648013 1600 1605 MMP-7 Gene 4316 18648013 1646 1659 breast cancer Disease D001943 15866551|t|Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. 15866551|t|BACKGROUND: Recent evidence documents that cannabis use by young people is a modest statistical risk factor for psychotic symptoms in adulthood, such as hallucinations and delusions, as well as clinically significant schizophrenia. The vast majority of cannabis users do not develop psychosis, however, prompting us to hypothesize that some people are genetically vulnerable to the deleterious effects of cannabis. METHODS: In a longitudinal study of a representative birth cohort followed to adulthood, we tested why cannabis use is associated with the emergence of psychosis in a minority of users, but not in others. RESULTS: A functional polymorphism in the catechol-O-methyltransferase (COMT) gene moderated the influence of adolescent cannabis use on developing adult psychosis. Carriers of the COMT valine158 allele were most likely to exhibit psychotic symptoms and to develop schizophreniform disorder if they used cannabis. Cannabis use had no such adverse influence on individuals with two copies of the methionine allele. CONCLUSIONS: These findings provide evidence of a gene x environment interaction and suggest that a role of some susceptibility genes is to influence vulnerability to environmental pathogens. 15866551 28 57 adolescent-onset cannabis use Environment 1312-D011618 15866551 67 76 psychosis Disease D011605 15866551 113 141 catechol-O-methyltransferase Gene 1312 15866551 112 130 psychotic symptoms Disease D011605 15866551 153 167 hallucinations Disease D006212 15866551 217 230 schizophrenia Disease D012559 15866551 283 292 psychosis Disease D011605 15866551 567 576 psychosis Disease D011605 15866551 662 690 catechol-O-methyltransferase Gene 1312 15866551 692 696 COMT Gene 1312 15866551 730 753 adolescent cannabis use Environment 1312-D011618 15866551 774 783 psychosis Disease D011605 15866551 801 805 COMT Gene 1312 15866551 851 869 psychotic symptoms Disease D011605 15866551 885 910 schizophreniform disorder Disease D011618 15866551 924 932 cannabis Environment 1312-D011618 20056625|t|Variation in the FGFR2 gene and the effect of a low-fat dietary pattern on invasive breast cancer. 20056625|t|BACKGROUND: The Women's Health Initiative dietary modification (DM) trial provided suggestive evidence of a benefit of a low-fat dietary pattern on breast cancer risk, with stronger evidence among women whose baseline diet was high in fat. Single nucleotide polymorphisms (SNP) in the FGFR2 gene relate strongly to breast cancer risk and could influence intervention effects. METHODS: All 48,835 trial participants were postmenopausal and ages 50 to 79 years at enrollment (1993-1998). We interrogated eight SNPs in intron 2 of the FGFR2 gene for 1,676 women who developed breast cancer during trial follow-up (1993-2005). Case-only analyses were used to estimate odds ratios for the DM intervention in relation to SNP genotype. RESULTS: Odds ratios for the DM intervention did not vary significantly with the genotype for any of the eight FGFR2 SNPs (P > or = 0.18). However, odds ratios varied (P < 0.05) with the genotype of six of these SNPs, among women having baseline percent of energy from fat in the upper quartile (> or =36.8%). This variation is most evident for SNP rs3750817, with odds ratios for the DM intervention at 0, 1, and 2 minor SNP alleles of 1.06 [95% confidence intervals (95% CI), 0.80-1.41], 0.53 (95% CI, 0.38-0.74), and 0.62 (95% CI, 0.33-1.15). The nominal significance level for this interaction is P = 0.005, and P = 0.03 following multiple testing adjustment, with most evidence deriving from hormone receptor-positive tumors. CONCLUSION: Invasive breast cancer odds ratios for a low-fat dietary pattern, among women whose usual diets are high in fat, seem to vary with SNP rs3750817 in the FGFR2 gene. 20056625 17 22 FGFR2 Gene 2263 20056625 84 97 breast cancer Disease D001943 20056625 148 161 breast cancer Disease D001943 20056625 285 290 FGFR2 Gene 2263 20056625 315 328 breast cancer Disease D001943 20056625 532 537 FGFR2 Gene 2263 20056625 573 586 breast cancer Disease D001943 20056625 840 845 FGFR2 Gene 2263 20056625 998 1023 fat in the upper quartile Environment 2263-D001943 20056625 1452 1458 tumors Disease D009369 20056625 1481 1494 breast cancer Disease D001943 20056625 1511 1536 a low-fat dietary pattern Environment 2263-D001943 20056625 1544 1583 women whose usual diets are high in fat Environment 2263-D001943 20056625 1624 1629 FGFR2 Gene 2263 26551148|t|Gene-environment interaction of genome-wide association study-identified susceptibility loci and meat-cooking mutagens in the etiology of renal cell carcinoma. 26551148|t|BACKGROUND: Meat-cooking mutagens may be associated with renal cell carcinoma (RCC) risk. In the current study, the authors examined associations between meat-cooking mutagens, genetic susceptibility variants, and risk of RCC. METHODS: The authors used 659 newly diagnosed RCC cases and 699 healthy controls to investigate the association between dietary intake of meat-cooking mutagens and RCC. They examined whether associations varied by risk factors for RCC and genetic susceptibility variants previously identified from genome-wide association studies. Odds ratios and 95% confidence intervals were estimated using tertiles of intake of dietary polycyclic aromatic hydrocarbons/heterocyclic amines. RESULTS: Dietary intake of the mutagenic compounds 2-amino-3,8-dimethylimidazo-(4,5-f) quinoxaline (MeIQx) and 2-amino-1 methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) were found to be significantly associated with an increased risk of RCC (odds ratios across tertiles: 1.00 [referent], 1.28 [95% confidence interval, 0.94-1.74], and 1.95 [95% confidence interval, 1.43-2.66] [P for trend <.001], respectively; and 1.00 [referent], 1.41 [95% confidence interval, 1.04-1.90], and 1.54 [95% confidence interval, 1.14-2.07] [P for trend =.02], respectively). The authors observed evidence of interactions between PhIP and RCC susceptibility variants in 2 genes: inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) (rs718314; multiplicative P for interaction = .03 and additive P for interaction =.002) and endothelial PAS domain-containing protein 1 (EPAS1) (rs7579899; additive P for interaction =.06). CONCLUSIONS: The intake of meat may increase the risk of RCC through mechanisms related to the cooking compounds MeIQx and PhIP. These associations may be modified by genetic susceptibility to RCC. Further research is necessary to understand the biological mechanisms underlying these interactions. 26551148 138 158 renal cell carcinoma Disease D002292 26551148 57 77 renal cell carcinoma Disease D002292 26551148 79 82 RCC Disease D002292 26551148 177 184 genetic Disease 1 26551148 222 225 RCC Disease D002292 26551148 273 276 RCC Disease D002292 26551148 391 394 RCC Disease D002292 26551148 458 461 RCC Disease D002292 26551148 466 473 genetic Disease 1 26551148 938 941 RCC Disease D002292 26551148 1312 1316 PhIP Environment 2034-D002292 26551148 1312 1316 PhIP Environment 3709-D002292 26551148 1321 1324 RCC Disease D002292 26551148 1361 1406 inositol 1,4,5-trisphosphate receptor, type 2 Gene 3709 26551148 1408 1413 ITPR2 Gene 3709 26551148 1552 1557 EPAS1 Gene 2034 26551148 1618 1632 intake of meat Environment 2034-D002292 26551148 1618 1632 intake of meat Environment 3709-D002292 26551148 1658 1661 RCC Disease D002292 26551148 1692 1724 cooking compounds MeIQx and PhIP Environment 2034-D002292 26551148 1692 1724 cooking compounds MeIQx and PhIP Environment 3709-D002292 26551148 1764 1771 genetic Disease 1 26551148 1790 1793 RCC Disease D002292 20975374|t|DNA repair gene X-ray repair cross complementing group 1 Arg194Trp polymorphism on the risk of lung cancer: a meta-analysis on 22 studies. 20975374|t|BACKGROUND: DNA repair gene X-ray repair cross complementing group 1 (XRCC1) Arg194Trp polymorphism has been investigated widely on lung cancer risk. However, the results are inconclusive. To derive a more precise estimation of the relationship between XRCC1 Arg194Trp polymorphism and lung cancer risk, we performed this meta-analysis. METHODS: An electronic search of the database PubMed, Embase, and Chinese National Knowledge Infrastructure was performed. The odds ratio (OR) was pooled by STATA 10.1. Subgroup analyses by ethnicity, gender, smoking, and histologic types of lung cancer were performed. RESULTS: Twenty-two studies including 7515 cases and 9560 controls were identified ultimately. The pooled OR for total population showed that homozygous Trp/Trp variant genotype could increase lung cancer risk compared with the homozygous wild Arg/Arg genotype (OR = 1.22, 95% confidence interval [CI] = 1.04-1.44, p = 0.01); however, heterozygote Arg/Trp variant genotype could decrease lung cancer risk (OR = 0.91, 95% CI = 0.85-0.99, p = 0.02). Subgroup analyses by ethnicity confirmed the result that homozygous Trp/Trp variant genotype increased lung cancer risk in Asians (OR = 1.19, 95% CI = 1.01-1.41, p = 0.04) but not in whites. It was interesting to find that both the heterozygote Arg/Trp and the combined Trp/Trp + Arg/Trp variant genotypes could decrease the risk of lung cancer in whites (OR = 0.83, 95% CI = 0.72-0.96, p = 0.01; OR = 0.85, 95% CI = 0.74-0.98, p = 0.03, respectively) but not in Asians. Subgroup analyses by gender, smoking, and histologic types of lung cancer did not indicate any significant difference between cases and controls, excepted for male population, which carried heterozygote Arg/Trp variant genotype that could decrease lung cancer risk (OR = 0.54, 95% CI = 0.31-0.95, p = 0.03). CONCLUSIONS: Homozygous Trp/Trp variant genotype of XRCC1 Arg194Trp polymorphism could increase lung cancer risk in total population, especially in Asians. However, the heterozygote Arg/Trp variant genotype might decrease the risk of lung cancer, especially in whites. 20975374 16 56 X-ray repair cross complementing group 1 Gene 7515 20975374 95 106 lung cancer Disease D008175 20975374 28 68 X-ray repair cross complementing group 1 Gene 7515 20975374 70 75 XRCC1 Gene 7515 20975374 132 143 lung cancer Disease D008175 20975374 253 258 XRCC1 Gene 7515 20975374 286 297 lung cancer Disease D008175 20975374 579 590 lung cancer Disease D008175 20975374 800 811 lung cancer Disease D008175 20975374 995 1006 lung cancer Disease D008175 20975374 1158 1169 lung cancer Disease D008175 20975374 1178 1184 Asians Environment 7515-D008175 20975374 1388 1399 lung cancer Disease D008175 20975374 1403 1409 whites Environment 7515-D008175 20975374 1588 1599 lung cancer Disease D008175 20975374 1685 1700 male population Environment 7515-D008175 20975374 1774 1785 lung cancer Disease D008175 20975374 1886 1891 XRCC1 Gene 7515 20975374 1930 1941 lung cancer Disease D008175 20975374 1982 1988 Asians Environment 7515-D008175 20975374 2068 2079 lung cancer Disease D008175 20975374 2095 2101 whites Environment 7515-D008175 17413111|t|A functional 19-base pair deletion polymorphism of dihydrofolate reductase (DHFR) and risk of breast cancer in multivitamin users. 17413111|t|BACKGROUND: Dihydrofolate reductase (DHFR) converts dihydrofolate (DHF) into tetrahydrofolate (THF) and plays an essential role in cell metabolism and cellular growth. Folic acid from multivitamins needs to be reduced by DHFR before it participates in cellular reactions. OBJECTIVES: We examined the relation of a 19-base pair (bp) deletion polymorphism of the DHFR gene with the risk of breast cancer by using data from the Long Island Breast Cancer Study Project, a population-based case-control study. We also investigated the transcriptional effect of this deletion polymorphism. DESIGN: Dietary data and habitual use of multivitamins were assessed from a modified Block food-frequency questionnaire (FFQ). Genotypes of DHFR were ascertained from 1062 case subjects and 1099 control subjects by allele-specific polymerase chain reaction. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% CIs. RESULT: Although the DHFR 19-bp deletion polymorphism was not associated with overall breast cancer risk, we observed a borderline significant additive interaction (P = 0.06) between the DHFR genotype and multivitamin use. The -19-bp allele was associated with greater breast cancer risk in multivitamin users (51.2% of the study population) with an OR of 1.26 (95% CI: 0.96, 1.66) and 1.52 (95% CI: 1.08, 2.13) for the +/- and -/- genotypes, respectively (P for trend = 0.02) than in multivatimin nonusers. A dose-dependent relation (P for trend < 0.001) between DHFR expression and the deletion genotype was observed. Compared with the subjects with the 19-bp +/+ genotype, subjects with the -/- genotype had 4.8-fold DHFR mRNA levels. CONCLUSIONS: The DHFR 19-bp deletion polymorphism affects the transcription of DHFR gene in humans. Multivitamin supplements may place a subgroup of women (ie, those with the -19-bp allele) at elevated risk of developing breast cancer. 17413111 51 74 dihydrofolate reductase Gene 1719 17413111 76 80 DHFR Gene 1719 17413111 94 107 breast cancer Disease D001943 17413111 12 35 Dihydrofolate reductase Gene 1719 17413111 37 41 DHFR Gene 1719 17413111 221 225 DHFR Gene 1719 17413111 361 365 DHFR Gene 1719 17413111 388 401 breast cancer Disease D001943 17413111 437 450 Breast Cancer Disease D001943 17413111 724 728 DHFR Gene 1719 17413111 949 953 DHFR Gene 1719 17413111 1014 1027 breast cancer Disease D001943 17413111 1115 1119 DHFR Gene 1719 17413111 1197 1210 breast cancer Disease D001943 17413111 1219 1237 multivitamin users Environment 1719-D001943 17413111 1492 1496 DHFR Gene 1719 17413111 1648 1652 DHFR Gene 1719 17413111 1683 1687 DHFR Gene 1719 17413111 1745 1749 DHFR Gene 1719 17413111 1887 1900 breast cancer Disease D001943 19124497|t|Cruciferous vegetable consumption and lung cancer risk: a systematic review. 19124497|t|BACKGROUND: Cruciferous vegetables, rich in isothiocyanates, may protect against lung cancer. Glutathione S-transferases are important in metabolizing isothiocyanates; hence, variants in GST genes may modify the association between cruciferous vegetable intake and lung cancer. We carried out a systematic review to characterize the association between cruciferous vegetable intake and lung cancer risk, with an emphasis on the potential interaction between cruciferous vegetables and GSTM1 and GSTT1 gene variants. METHODS: A search of the epidemiologic literature through December 2007 was conducted using 15 bibliographic databases without language restrictions. Thirty studies on the association between lung cancer and either total cruciferous vegetable consumption (6 cohort and 12 case-control studies) or specific cruciferous vegetables (1 cohort and 11 case-control studies) were included. RESULTS: The risk for lung cancer among those in the highest category of total cruciferous vegetable intake was 22% lower in case-control studies [random-effects pooled odds ratio, 0.78; 95% confidence interval (95% CI), 0.70-0.88] and 17% lower in cohort studies (pooled relative risk, 0.83; 95% CI, 0.62-1.08) compared with those in the lowest category of intake. The strongest inverse association of total cruciferous vegetable intake with lung cancer risk was seen among individuals with GSTM1 and GSTT1 double null genotypes (odds ratio, 0.41; 95% CI, 0.26-0.65; P for interaction = 0.01). CONCLUSIONS: Epidemiologic evidence suggests that cruciferous vegetable intake may be weakly and inversely associated with lung cancer risk. Because of a gene-diet interaction, the strongest inverse association was among those with homozygous deletion for GSTM1 and GSTT1. 19124497 38 49 lung cancer Disease D008175 19124497 81 92 lung cancer Disease D008175 19124497 265 276 lung cancer Disease D008175 19124497 386 397 lung cancer Disease D008175 19124497 485 490 GSTM1 Gene 2944 19124497 495 500 GSTT1 Gene 2952 19124497 708 719 lung cancer Disease D008175 19124497 921 932 lung cancer Disease D008175 19124497 1302 1336 total cruciferous vegetable intake Environment 2952-D008175 19124497 1302 1336 total cruciferous vegetable intake Environment 2944-D008175 19124497 1342 1353 lung cancer Disease D008175 19124497 1391 1396 GSTM1 Gene 2944 19124497 1401 1406 GSTT1 Gene 2952 19124497 1544 1572 cruciferous vegetable intake Environment 2952-D008175 19124497 1544 1572 cruciferous vegetable intake Environment 2944-D008175 19124497 1617 1628 lung cancer Disease D008175 19124497 1750 1755 GSTM1 Gene 2944 19124497 1760 1765 GSTT1 Gene 2952 16192345|t|Associations between breast cancer risk and the catalase genotype, fruit and vegetable consumption, and supplement use. 16192345|t|Observed weak or null associations between fruit and vegetable intake and breast cancer risk could be due to heterogeneity in endogenous antioxidant capabilities. The authors evaluated potential relations between a functional polymorphism in catalase, an antioxidant enzyme, and breast cancer risk, particularly in relation to fruit and vegetable intake and supplement use. Women (1,008 cases and 1,056 controls) in the Long Island Breast Cancer Study Project (1996-1997) were interviewed, completed a food frequency questionnaire, and provided blood for genotyping. The high-activity catalase CC genotype was associated with an overall 17% reduction in risk of breast cancer compared with having at least one variant T allele (odds ratio = 0.83, 95% confidence interval: 0.69, 1.00). Vegetable and, particularly, fruit consumption contributed to the decreased risk associated with the catalase CC genotype. Associations were more pronounced among women who did not use vitamin supplements, with a significant multiplicative interaction (p(interaction) = 0.02) for the CC genotype and high fruit intake (odds ratio = 0.59, 95% confidence interval: 0.38, 0.89), and there was no association among supplement users. These results indicate the importance of diet, rather than supplement use, in concert with endogenous antioxidant capabilities, in the reduction of breast cancer risk. CC genotypes were prevalent in approximately 64% of controls; thus, the preventive potential for fruit consumption has widespread implications. 16192345 21 34 breast cancer Disease D001943 16192345 48 56 catalase Gene 847 16192345 74 87 breast cancer Disease D001943 16192345 242 250 catalase Gene 847 16192345 279 292 breast cancer Disease D001943 16192345 585 593 catalase Gene 847 16192345 662 675 breast cancer Disease D001943 16192345 785 794 Vegetable Environment 847-D001943 16192345 814 831 fruit consumption Environment 847-D001943 16192345 886 894 catalase Gene 847 16192345 954 989 who did not use vitamin supplements Environment 847-D001943 16192345 1085 1102 high fruit intake Environment 847-D001943 16192345 1362 1375 breast cancer Disease D001943 16192345 1479 1496 fruit consumption Environment 847-D001943 20676096|t|Genome-wide association study identifies 1p36.22 as a new susceptibility locus for hepatocellular carcinoma in chronic hepatitis B virus carriers. 20676096|t|To identify susceptibility variants for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we conducted a genome-wide association study by genotyping 440,794 SNPs in 355 chronic HBV carriers with HCC and 360 chronic HBV carriers without HCC, all of Chinese ancestry. We identified one intronic SNP (rs17401966) in KIF1B on chromosome 1p36.22 that was highly associated with HBV-related HCC and confirmed this association in five additional independent samples, consisting of 1,962 individuals with HCC, 1,430 control subjects and 159 family trios. Across the six studies, the association with rs17401966 was highly statistically significant (joint odds ratio = 0.61, P = 1.7 x 10(-18)). In addition to KIF1B, the association region tagged two other plausible causative genes, UBE4B and PGD. Our findings provide evidence that the 1p36.22 locus confers susceptibility to HBV-related HCC, and suggest that KIF1B-, UBE4B- or PGD-related pathways might be involved in the pathogenesis of this malignancy. 20676096 83 107 hepatocellular carcinoma Disease D006528 20676096 119 130 hepatitis B Disease D006509 20676096 119 136 hepatitis B virus Disease D006509 20676096 40 51 hepatitis B Disease D006509 20676096 72 96 hepatocellular carcinoma Disease D006528 20676096 98 101 HCC Disease D006528 20676096 209 212 HCC Disease D006528 20676096 250 253 HCC Disease D006528 20676096 327 332 KIF1B Gene 23095 20676096 387 390 HBV Environment 23095-D006528 20676096 399 402 HCC Disease D006528 20676096 511 514 HCC Disease D006528 20676096 715 720 KIF1B Gene 23095 20676096 789 794 UBE4B Gene 10277 20676096 799 802 PGD Gene 26227 20676096 883 886 HBV Environment 23095-D006528 20676096 895 898 HCC Disease D006528 20676096 917 922 KIF1B Gene 23095 20676096 925 930 UBE4B Gene 10277 20676096 935 938 PGD Gene 26227 20676096 1002 1012 malignancy Disease D009369 17372271|t|Polymorphisms of one-carbon-metabolizing genes and risk of breast cancer in a population-based study. 17372271|t|One-carbon metabolism facilitates the crosstalk between genetic and epigenetic processes and plays critical roles in both DNA methylation and DNA synthesis, making it a good candidate for studying the risk of breast cancer. We previously reported that polymorphisms in methylenetetrahydrofolate reductase (MTHFR) in one-carbon pathway were associated with breast cancer risk in the population-based Long Island Breast Cancer Study Project. Herein, we systematically investigated putatively functional polymorphisms of seven other one-carbon-metabolizing genes in relation to the breast cancer risk in the same population. Except for a slight indication of increased risk of breast cancer associated with the double repeat (2R) allele in the thymidylate synthase (TYMS) 5'-untranslated region (UTR) (P, trend = 0.07), polymorphisms in the other six genes did not substantially modify the risk of breast cancer, or did they modify the risk associated with dietary intakes of folate and related B vitamins. However, we observed a significant multiplicative interaction between the MTHFR 677C>T and the TYMS 5'-UTR polymorphisms (P = 0.02). We used a recursive partitioning method, RTREE, in an attempt to tease out important or rate-limiting genes encoding these intricately related enzymes. Results from RTREE analyses indicate that MTHFR and TYMS are the two leading rate-limiting enzymes in the pathway, consistent with our epidemiological findings. Our findings underscore the importance of one-carbon metabolism in breast cancer etiology. Although the pathway is a network of interrelated enzymes, redundancy exists; evaluating the rate-limiting enzyme and its interaction with environment and other genes within the same pathway is critical in assessing breast cancer risk. 17372271 59 72 breast cancer Disease D001943 17372271 209 222 breast cancer Disease D001943 17372271 269 304 methylenetetrahydrofolate reductase Gene 4524 17372271 306 311 MTHFR Gene 4524 17372271 356 369 breast cancer Disease D001943 17372271 579 592 breast cancer Disease D001943 17372271 674 687 breast cancer Disease D001943 17372271 741 761 thymidylate synthase Gene 7298 17372271 763 767 TYMS Gene 7298 17372271 895 908 breast cancer Disease D001943 17372271 954 1002 dietary intakes of folate and related B vitamins Environment 4524-D001943 17372271 1078 1083 MTHFR Gene 4524 17372271 1099 1103 TYMS Gene 7298 17372271 1331 1336 MTHFR Gene 4524 17372271 1341 1345 TYMS Gene 7298 17372271 1517 1530 breast cancer Disease D001943 17372271 1757 1770 breast cancer Disease D001943 16006998|t|Polymorphisms of methionine synthase and methionine synthase reductase and risk of lung cancer: a case-control analysis. 16006998|t|Although tobacco is the major lung cancer risk factor, folate deficiency has also been implicated as a risk. Methionine synthase (MS; gene symbol, MTR) and methionine synthase reductase (MSR; gene symbol, MTRR) play important roles in the folate metabolism pathway. It was hypothesized that polymorphisms of MTR and MTRR are associated with lung cancer risk and interact with dietary intake of folate-related nutrients in lung cancer etiology. In a hospital-based, case-control study of 1,035 lung cancer cases and 1,148 controls of non-Hispanic whites, frequency matched by age, sex, ethnicity and smoking status, the MTR 2756A>G and MTRR 66A>G polymorphisms were genotyped. It was found that the MTRRG allele was associated with a significantly increased lung cancer risk [adjusted odd ratio (OR)=1.34, 95% confidence interval (CI)=1.06-1.70 for the AG genotype and OR=1.39, 95% CI=1.08-1.78 for the GG genotype compared to the AA genotype]. Further analysis suggested some evidence of gene-diet interactions between the MTRR 66A>G polymorphism and dietary intake of total folate and vitamin B12. When the two polymorphisms were evaluated together by the number of the variant alleles (i.e. the MTR2756G and MTRR66A), lung cancer risk was significantly increased in a dose-dependent manner (Ptrend=0.045). The risk of lung cancer was 1.29 (0.98-1.69) for one variant allele, and 1.36 (1.04-1.77) for two or more variant alleles compared to the wild-type (0 variant allele) genotype. In conclusion, our data provide evidence supporting the association between the MTR 2756A>G and MTRR 66A>G polymorphisms and lung cancer risk, which may be modulated by dietary nutrient intake. 16006998 41 70 methionine synthase reductase Gene 4552 16006998 83 94 lung cancer Disease D008175 16006998 30 41 lung cancer Disease D008175 16006998 156 185 methionine synthase reductase Gene 4552 16006998 187 190 MSR Gene 4552 16006998 205 209 MTRR Gene 4552 16006998 316 320 MTRR Gene 4552 16006998 341 352 lung cancer Disease D008175 16006998 422 433 lung cancer Disease D008175 16006998 493 504 lung cancer Disease D008175 16006998 635 639 MTRR Gene 4552 16006998 757 768 lung cancer Disease D008175 16006998 1023 1027 MTRR Gene 4552 16006998 1051 1097 dietary intake of total folate and vitamin B12 Environment 4552-D008175 16006998 1210 1214 MTRR Gene 4552 16006998 1220 1231 lung cancer Disease D008175 16006998 1320 1331 lung cancer Disease D008175 16006998 1581 1585 MTRR Gene 4552 16006998 1610 1621 lung cancer Disease D008175 16006998 1654 1677 dietary nutrient intake Environment 4552-D008175 15879416|t|CD14 tobacco gene-environment interaction modifies asthma severity and immunoglobulin E levels in Latinos with asthma. 15879416|t|BACKGROUND: A recent family-based genomewide screen revealed linkage between the 5q31 region and the diagnosis of asthma, but only in those exposed to environmental tobacco smoke (ETS). Among the candidate genes in this region is CD14. METHODS: To determine whether polymorphisms in the CD14 gene are related to this gene-by-environment interaction in Latinos, we used both family-based and cross-sectional cohort analysis to test for interactions between CD14 genotypes/haplotypes, exposure to ETS, and asthma-related phenotypes in 659 Mexican and Puerto Rican families. RESULTS: We identified 21 single nucleotide polymorphisms (SNPs) in the CD14 gene by sequencing 72 Puerto Ricans, Mexicans, and African Americans with asthma. Three SNPs, -810, -159, and +1437, were further genotyped in families with asthma. Among all subjects with asthma exposed to ETS, without regard to ethnicity, CD14 +1437 genotypes were associated with asthma severity. SNP +1437 GG or GC genotypes were significantly associated with lower baseline FEV1 using both family-based (p = 0.0009) and cross-sectional cohort (p = 0.03) analyses. Subjects with asthma with the GG or GC genotypes who were exposed to ETS had mean baseline FEV1 (% predicted) values 8.6% lower than subjects not exposed to ETS (p = 0.03). As previously observed in whites, we found an interaction between plasma IgE levels, SNP -159 genotypes, and ETS exposure (p = 0.0002). The lowest IgE levels were in those subjects with the TT genotype and who were exposed to ETS regardless of ethnicity. CONCLUSIONS: Our data suggest a gene-by-environment interaction between CD14 genotypes and ETS, which affects pulmonary function and IgE levels among Latinos with asthma. 15879416 0 4 CD14 Gene 929 15879416 5 12 tobacco Environment 929-D001249 15879416 51 57 asthma Disease D001249 15879416 111 117 asthma Disease D001249 15879416 114 120 asthma Disease D001249 15879416 230 234 CD14 Gene 929 15879416 287 291 CD14 Gene 929 15879416 456 460 CD14 Gene 929 15879416 504 510 asthma Disease D001249 15879416 644 648 CD14 Gene 929 15879416 723 729 asthma Disease D001249 15879416 806 812 asthma Disease D001249 15879416 838 844 asthma Disease D001249 15879416 890 894 CD14 Gene 929 15879416 932 938 asthma Disease D001249 15879416 1132 1138 asthma Disease D001249 15879416 1187 1190 ETS Environment 929-D001249 15879416 1364 1367 IgE Gene 3497 15879416 1438 1441 IgE Gene 3497 15879416 1618 1622 CD14 Gene 929 15879416 1637 1640 ETS Environment 929-D001249 15879416 1656 1674 pulmonary function Disease OMIM:608852 15879416 1679 1682 IgE Gene 3497 15879416 1709 1715 asthma Disease D001249 20537530|t|Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: a meta-analysis. 20537530|t|BACKGROUND: Women with BRCA1 or BRCA2 mutations are at increased risk of breast and ovarian cancer. Oral contraceptives (OC) use has been associated with a reduction in ovarian cancer risk and with a moderately increased breast cancer risk, which tends to level off in the few years after stopping. The association between oral contraceptive and BRCA1 or BRCA2 gene mutations carriers is unclear. METHODS: We performed a comprehensive literature search updated to March 2010 of studies on the associations between OC users and breast or ovarian cancer for ascertained BRCA1/2 carriers. We obtained summary risk estimated for ever OC users, for duration of use and time since stopping. RESULTS: A total of 2855 breast cancer cases and 1503 ovarian cancer cases, carrying an ascertained BRCA1/2 mutation, were included in our meta-analyses, based on overall 18 studies. Use of OC was associated with a significant reduced risk of ovarian cancer for BRCA1/2 carriers (summary relative risk (SRR)=0.50; 95% confidence interval (CI), 0.33-0.75). We also observed a significant 36% risk reduction for each additional 10 years of OC use (SRR: 0.64; 95% CI, 0.53-0.78; P trend<0.01). We found no evidence of a significant association between OC and breast cancer risk in carriers (SRR: 1.13; 95% CI, 0.88-1.45) and with duration of use. OC formulations used before 1975 were associated with a significant increased risk of breast cancer (SRR: 1.47; 95% 1.06, 2.04), but no evidence of a significant association was found with use of more recent formulations (SRR: 1.17; 95% 0.74, 1.86). CONCLUSIONS: OC users carrying an ascertained BRCA1/2 mutation have a reduced risk of ovarian cancer, proportional to the duration of use. There is no evidence that recent OC formulations increase breast cancer risk in carriers. 20537530 27 51 breast or ovarian cancer Disease D001943 20537530 27 51 breast or ovarian cancer Disease D010051 20537530 60 67 BRCA1/2 Gene 675 20537530 60 67 BRCA1/2 Gene 672 20537530 23 28 BRCA1 Gene 672 20537530 32 37 BRCA2 Gene 675 20537530 73 98 breast and ovarian cancer Disease D061325 20537530 169 183 ovarian cancer Disease D010051 20537530 221 234 breast cancer Disease D001943 20537530 346 351 BRCA1 Gene 672 20537530 355 360 BRCA2 Gene 675 20537530 527 551 breast or ovarian cancer Disease D001943 20537530 527 551 breast or ovarian cancer Disease D010051 20537530 568 575 BRCA1/2 Gene 675 20537530 568 575 BRCA1/2 Gene 672 20537530 710 723 breast cancer Disease D001943 20537530 739 753 ovarian cancer Disease D010051 20537530 785 790 BRCA1 Gene 672 20537530 868 877 Use of OC Environment 672-D010051 20537530 868 877 Use of OC Environment 675-D010051 20537530 928 942 ovarian cancer Disease D010051 20537530 947 954 BRCA1/2 Gene 675 20537530 947 954 BRCA1/2 Gene 672 20537530 1100 1129 additional 10 years of OC use Environment 672-D010051 20537530 1100 1129 additional 10 years of OC use Environment 675-D010051 20537530 1241 1254 breast cancer Disease D001943 20537530 1415 1428 breast cancer Disease D001943 20537530 1592 1600 OC users Environment 672-D010051 20537530 1592 1600 OC users Environment 675-D010051 20537530 1625 1630 BRCA1 Gene 672 20537530 1665 1679 ovarian cancer Disease D010051 20537530 1776 1789 breast cancer Disease D001943 17908995|t|Genetic variants in cell cycle control pathway confer susceptibility to lung cancer. 17908995|t|PURPOSE: To test the hypothesis that common sequence variants of cell cycle control genes may affect lung cancer predisposition. EXPERIMENTAL DESIGN: We explored lung cancer risk associations of 11 polymorphisms in seven cell cycle genes in a large case-control study including 1,518 Caucasian lung cancer patients and 1,518 controls. RESULTS: When individuals with variant-containing genotypes were compared with homozygous wild-type carriers, a significantly increased lung cancer risk was identified for polymorphisms in p53 intron 6 [rs1625895; odds ratio (OR), 1.29; 95% confidence interval (95% CI), 1.08-1.55] and in p27 5' untranslated region (UTR; rs34330; OR, 1.27; 95% CI, 1.01-1.60). Compared with homozygous wild-types, the homozygous variant genotypes of STK15 F31I and CCND1 G870A were associated with a significantly altered lung cancer risk with ORs of 0.58 (95% CI, 0.37-0.90) and 1.26 (95% CI, 1.03-1.53), respectively. To assess the cumulative effects of all the investigated polymorphisms on lung carcinogenesis, we conducted a combined analysis and found that compared with low-risk individuals with few adverse alleles, individuals with more adverse alleles had an increased risk in a significant dose-dependent manner (P(trend) = 0.041). This pattern was more evident in ever smokers (P(trend) = 0.037), heavy smokers (P(trend) = 0.020), and older subjects (P(trend) = 0.011). Higher-order gene-gene interactions were evaluated using the classification and regression tree analysis, which indicated that STK15 F31I and p53 intron 6 polymorphisms might be associated with lung carcinogenesis in never/light-smokers and heavy smokers, respectively. CONCLUSIONS: Our results suggest that cell cycle gene polymorphisms and smoking may function collectively to modulate the risk of lung cancer. 17908995 72 83 lung cancer Disease D008175 17908995 101 112 lung cancer Disease D008175 17908995 162 173 lung cancer Disease D008175 17908995 294 305 lung cancer Disease D008175 17908995 471 482 lung cancer Disease D008175 17908995 524 527 p53 Gene 7157 17908995 624 627 p27 Gene 3429 17908995 769 774 STK15 Gene 6790 17908995 784 789 CCND1 Gene 595 17908995 841 852 lung cancer Disease D008175 17908995 1018 1032 carcinogenesis Disease D063646 17908995 1295 1307 ever smokers Environment 3429-D008175 17908995 1295 1307 ever smokers Environment 595-D008175 17908995 1295 1307 ever smokers Environment 7157-D008175 17908995 1295 1307 ever smokers Environment 6790-D008175 17908995 1328 1341 heavy smokers Environment 3429-D008175 17908995 1328 1341 heavy smokers Environment 595-D008175 17908995 1328 1341 heavy smokers Environment 7157-D008175 17908995 1328 1341 heavy smokers Environment 6790-D008175 17908995 1366 1380 older subjects Environment 3429-D008175 17908995 1366 1380 older subjects Environment 595-D008175 17908995 1366 1380 older subjects Environment 7157-D008175 17908995 1366 1380 older subjects Environment 6790-D008175 17908995 1528 1533 STK15 Gene 6790 17908995 1543 1546 p53 Gene 7157 17908995 1600 1614 carcinogenesis Disease D063646 17908995 1618 1637 never/light-smokers Environment 7157-D008175 17908995 1618 1637 never/light-smokers Environment 6790-D008175 17908995 1642 1655 heavy smokers Environment 7157-D008175 17908995 1642 1655 heavy smokers Environment 6790-D008175 17908995 1743 1750 smoking Environment 3429-D008175 17908995 1743 1750 smoking Environment 595-D008175 17908995 1743 1750 smoking Environment 7157-D008175 17908995 1743 1750 smoking Environment 6790-D008175 17908995 1801 1812 lung cancer Disease D008175 17507620|t|Polymorphisms in the CYP19A1 (aromatase) gene and endometrial cancer risk in Chinese women. 17507620|t|Aromatase, encoded by the CYP19A1 gene, is a key enzyme in estradiol biosynthesis, which catalyzes the conversion of androstenedione and testosterone to estrone and estradiol, respectively. Given the critical role of estrogen in the development of endometrial cancer risk, we evaluated genetic polymorphisms of the CYP19A1 gene, including rs1065779, rs700519, rs28566535, rs752760, and rs1870050, in association with endometrial cancer in a population-based case-control study conducted in Shanghai, China. Genotypes of 1,040 incident endometrial cancer cases and 1,031 frequency-matched controls were included in the study. We applied a logistic regression model to derive adjusted odds ratios (OR) and their 95% confidence intervals (95% CI). Six common haplotypes with a frequency >or=5% were estimated; the highest frequency haplotype was GCACA (27.8% in cases and 26.2% in controls). We observed an inverse association between CYP19A1 haplotype TCATC and endometrial cancer in our population (OR, 0.76; 95% CI, 0.62-0.92). An inverse association was found between endometrial cancer and single nucleotide polymorphism rs1870050 in the promoter region with ORs of 0.81 (95% CI, 0.68-0.97) and 0.58 (95% CI, 0.42-0.80) for the AC and CC genotypes, respectively. We observed a multiplicative interaction between single nucleotide polymorphism rs700519 and body mass index among postmenopausal women (P = 0.01), with stronger associations between rs700519 genotypes and endometrial cancer risk among heavier (body mass index, >or=25) postmenopausal women. In summary, our data show that polymorphisms in the CYP19A1 gene may contribute to endometrial carcinogenesis. 17507620 21 28 CYP19A1 Gene 1588 17507620 50 68 endometrial cancer Disease D016889 17507620 26 33 CYP19A1 Gene 1588 17507620 248 266 endometrial cancer Disease D016889 17507620 315 322 CYP19A1 Gene 1588 17507620 417 435 endometrial cancer Disease D016889 17507620 535 553 endometrial cancer Disease D016889 17507620 932 939 CYP19A1 Gene 1588 17507620 960 978 endometrial cancer Disease D016889 17507620 1069 1087 endometrial cancer Disease D016889 17507620 1358 1373 body mass index Environment 1588-D016889 17507620 1471 1489 endometrial cancer Disease D016889 17507620 1501 1555 heavier (body mass index, >or=25) postmenopausal women Environment 1588-D016889 17507620 1609 1616 CYP19A1 Gene 1588 17507620 1652 1666 carcinogenesis Disease D063646 16624829|t|Effects of glutathione S-transferase A1 (GSTA1) genotype and potential modifiers on breast cancer risk. 16624829|t|Glutathione S-transferases (GSTs) are phase II enzymes that are involved in the detoxification of a wide range of carcinogens. The novel GSTA1*A and GSTA1*B genetic polymorphism results in differential expression, with lower transcriptional activation of GSTA1*B (variant) than that of GSTA1*A (common) allele. Considering that cruciferous vegetables induce GSTs, which metabolize tobacco smoke carcinogens, we hypothesized that the variant GSTA1*B genotype may predispose women to breast cancer, particularly among low cruciferous vegetable consumers and among smokers. Thus, we evaluated potential relationships between GSTA1 polymorphisms and breast cancer risk, in relation to vegetable consumption and smoking status in the Long Island Breast Cancer Study Project (1996-1997), a population-based case-control study. Genotyping (1036 cases and 1089 controls) was performed, and putative breast cancer risk factors and usual dietary intakes were assessed. Having GSTA1*A/*B or *B/*B genotypes was not associated with increased breast cancer risk, compared to having the common *A/*A genotype. However, among women in the lowest two tertiles of cruciferous vegetable consumption, *B/*B genotypes were associated with increased risk (OR (95% CI)=1.73 (1.10-2.72) for 0-1 servings/week), compared to women with *A/*A genotypes. Among women with *B/*B genotypes, a significant inverse trend between cruciferous vegetable consumption and breast cancer risk was observed (P for trend=0.05), and higher consumption (4+ servings/week) ameliorated the increased risk associated with the genotype. Current smokers with *B/*B genotypes had a 1.89-fold increase in risk (OR (95% CI)=1.89 (1.09-3.25)), compared with never smokers with *A/*A genotypes. These data indicate that GSTA1 genotypes related to reduced GSTA1 expression are associated with increased breast cancer primarily among women with lower consumption of cruciferous vegetables and among current smokers. 16624829 11 39 glutathione S-transferase A1 Gene 2938 16624829 41 46 GSTA1 Gene 2938 16624829 84 97 breast cancer Disease D001943 16624829 137 142 GSTA1 Gene 2938 16624829 149 154 GSTA1 Gene 2938 16624829 255 260 GSTA1 Gene 2938 16624829 286 291 GSTA1 Gene 2938 16624829 441 446 GSTA1 Gene 2938 16624829 482 495 breast cancer Disease D001943 16624829 622 627 GSTA1 Gene 2938 16624829 646 659 breast cancer Disease D001943 16624829 891 904 breast cancer Disease D001943 16624829 966 971 GSTA1 Gene 2938 16624829 1030 1043 breast cancer Disease D001943 16624829 1120 1180 the lowest two tertiles of cruciferous vegetable consumption Environment 2938-D001943 16624829 1398 1431 cruciferous vegetable consumption Environment 2938-D001943 16624829 1448 1461 breast cancer Disease D001943 16624829 1603 1618 Current smokers Environment 2938-D001943 16624829 1780 1785 GSTA1 Gene 2938 16624829 1815 1820 GSTA1 Gene 2938 16624829 1862 1875 breast cancer Disease D001943 16624829 1903 1946 lower consumption of cruciferous vegetables Environment 2938-D001943 16624829 1957 1972 current smokers Environment 2938-D001943 18714187|t|Methylenetetrahydrofolate reductase polymorphisms and susceptibility to gastric cancer in Chinese populations: a meta-analysis. 18714187|t|Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene are thought to have significant effects on folate metabolism and, thus, on cancer risk, but the reported results are not always consistent. In this meta-analysis including 2165 patients and 3279 controls, we assessed reported studies of associations between polymorphisms of MTHFR and susceptibility to gastric cancer in Chinese populations. An increased risk was found for MTHFR C677T in the meta-analysis [odds ratio (OR): 1.42; 95% confidence interval (CI): 1.24-1.62]. No association resulted for MTHFR A1298C (OR: 0.95; 95% CI: 0.78-1.17). Results from the subgroup analyses showed an increased risk for individuals with low (OR: 1.50; 95% CI: 1.18-1.91) versus high (OR: 1.21; 95% CI: 0.98-1.51) folate levels. The sensitivity analysis and publication bias diagnostics confirmed the reliability and stability of this meta-analysis. Overall, these findings support the hypothesis that folate plays a role in gastric carcinogenesis. Regarding cardia or noncardia gastric cancer, more studies are required for definite conclusions, as the number of studies is relatively small. 18714187 0 35 Methylenetetrahydrofolate reductase Gene 4524 18714187 72 86 gastric cancer Disease D013274 18714187 25 60 methylenetetrahydrofolate reductase Gene 4524 18714187 62 67 MTHFR Gene 4524 18714187 149 155 cancer Disease D009369 18714187 349 354 MTHFR Gene 4524 18714187 377 391 gastric cancer Disease D013274 18714187 448 453 MTHFR Gene 4524 18714187 575 580 MTHFR Gene 4524 18714187 776 789 folate levels Environment 4524-D013274 18714187 964 970 folate Environment 4524-D013274 18714187 995 1009 carcinogenesis Disease D063646 18714187 1021 1027 cardia Disease 1 18714187 1041 1055 gastric cancer Disease D013274 22831980|t|Confirmation that the AKT1 (rs2494732) genotype influences the risk of psychosis in cannabis users. 22831980|t|BACKGROUND: Cannabis use is associated with an increased risk of psychosis. One study has suggested that genetic variation in the AKT1 gene might influence this effect. METHODS: In a case-control study of 489 first-episode psychosis patients and 278 control subjects, we investigated the interaction between variation at the AKT1 rs2494732 single nucleotide polymorphism and cannabis use in increasing the risk of psychosis. RESULTS: The rs2494732 locus was not associated with an increased risk of a psychotic disorder, with lifetime cannabis use, or with frequency of use. We did, however, find that the effect of lifetime cannabis use on risk of psychosis was significantly influenced by the rs2494732 locus (likelihood ratio statistic for the interaction = 8.54; p = .014). Carriers of the C/C genotype with a history of cannabis use showed a greater than twofold increased likelihood of a psychotic disorder (odds ratio = 2.18 [95% confidence interval: 1.12, 4.31]) when compared with users who were T/T carriers. Moreover, the interaction between the rs2494732 genotype and frequency of use was also significant at the 5% level (likelihood ratio = 13.39; p = .010). Among daily users, C/C carriers demonstrated a sevenfold increase in the odds of psychosis compared with T/T carriers (odds ratio = 7.23 [95% confidence interval: 1.37, 38.12]). CONCLUSIONS: Our findings provide strong support for the initial report that genetic variation at rs2494732 of AKT1 influences the risk of developing a psychotic disorder in cannabis users. 22831980 22 26 AKT1 Gene 207 22831980 71 80 psychosis Disease D011605 22831980 71 98 psychosis in cannabis users Disease D011605 22831980 65 74 psychosis Disease D011605 22831980 130 134 AKT1 Gene 207 22831980 223 232 psychosis Disease D011605 22831980 325 329 AKT1 Gene 207 22831980 414 423 psychosis Disease D011605 22831980 501 519 psychotic disorder Disease D011618 22831980 616 637 lifetime cannabis use Environment 207-D011605 22831980 616 637 lifetime cannabis use Environment 207-D011618 22831980 649 658 psychosis Disease D011605 22831980 812 837 a history of cannabis use Environment 207-D011605 22831980 812 837 a history of cannabis use Environment 207-D011618 22831980 894 912 psychotic disorder Disease D011618 22831980 1080 1096 frequency of use Environment 207-D011605 22831980 1080 1096 frequency of use Environment 207-D011618 22831980 1178 1189 daily users Environment 207-D011605 22831980 1178 1189 daily users Environment 207-D011618 22831980 1253 1262 psychosis Disease D011605 22831980 1461 1465 AKT1 Gene 207 22831980 1502 1520 psychotic disorder Disease D011618 22831980 1524 1538 cannabis users Environment 207-D011605 22831980 1524 1538 cannabis users Environment 207-D011618 16702380|t|NAD(P)H:quinone oxidoreductase 1 (NQO1) Pro187Ser polymorphism and the risk of lung, bladder, and colorectal cancers: a meta-analysis. 16702380|t|UNLABELLED: NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytosolic enzyme that catalyzes the two-electron reduction of quinoid compounds into hydroquinones, their less toxic form. A sequence variant at position 609 (C --> T) in the NQO1 gene encodes an enzyme with reduced quinone reductase activity in vitro and thus was hypothesized to affect cancer susceptibility. We conducted meta-analyses focusing on three cancer sites (lung, bladder, and colorectum) to summarize the findings from the current literature and to explore sources of heterogeneity. RESULTS: There is no clear association between the NQO1 Pro187Ser polymorphism and lung cancer risk in the three ethnic groups examined: odds ratio (OR(White)) C/T + T/T versus C/C = 1.04 [95% confidence interval (95% CI), 0.96-1.13], OR(Asian) = 0.99 (95% CI, 0.72-1.34), and OR(Blacks) = 0.95 (95% CI, 0.66-1.36). However, a modestly increased risk was suggested for the variant homozygotes in whites (OR T/T versus C/C, 1.19; 95% CI, 0.94-1.50). Analysis excluding one outlier study suggested the variant allele may be associated with reduced lung cancer risk in Asians. Meta-analyses for bladder and colorectal cancer suggested a statistically significant association with the variant genotypes in whites. In stratified analyses, the NQO1 Pro187Ser variant genotypes were associated with slightly increased lung cancer risk in white ever smokers but not in white never smokers and were mainly associated with a reduced risk of lung adenocarcinoma but not squamous cell carcinoma in Asians. CONCLUSIONS: Results from our meta-analyses suggest that the variant NQO1 Pro187Ser genotype may affect individual susceptibility to lung, bladder, and colorectal cancer. Such effects of the NQO1 polymorphism seem to be modified by ethnicity and smoking status. 16702380 0 32 NAD(P)H:quinone oxidoreductase 1 Gene 1728 16702380 34 38 NQO1 Gene 1728 16702380 98 116 colorectal cancers Disease D015179 16702380 12 44 NAD(P)H:quinone oxidoreductase 1 Gene 1728 16702380 46 50 NQO1 Gene 1728 16702380 232 236 NQO1 Gene 1728 16702380 345 351 cancer Disease D009369 16702380 413 419 cancer Disease D009369 16702380 604 608 NQO1 Gene 1728 16702380 636 647 lung cancer Disease D008175 16702380 949 955 whites Environment 1728-D008175 16702380 1099 1110 lung cancer Disease D008175 16702380 1157 1174 colorectal cancer Disease D015179 16702380 1255 1261 whites Environment 1728-D015179 16702380 1291 1295 NQO1 Gene 1728 16702380 1364 1375 lung cancer Disease D008175 16702380 1384 1402 white ever smokers Environment 1728-D008175 16702380 1484 1503 lung adenocarcinoma Disease C538231 16702380 1512 1535 squamous cell carcinoma Disease D002294 16702380 1539 1545 Asians Environment 1728-C538231 16702380 1616 1620 NQO1 Gene 1728 16702380 1699 1716 colorectal cancer Disease D015179 16702380 1738 1742 NQO1 Gene 1728 16702380 1779 1788 ethnicity Environment 1728-D015179 16702380 1779 1788 ethnicity Environment 1728-D008175 16702380 1779 1788 ethnicity Environment 1728-C538231 16702380 1793 1807 smoking status Environment 1728-D008175 23203414|t|Association between CYP2A6 genetic polymorphisms and lung cancer: a meta-analysis of case-control studies. 23203414|t|Cytochrome P450 2A6 (CYP2A6) is an enzyme responsible for the metabolism of nicotine and some tobacco-specific carcinogens (such as N-nitrosamines). CYP2A6 genetic variations are associated with the activity of the CYP2A6 enzyme, which affects smoking behavior and the rate at which some tobacco-specific carcinogens are metabolized, which in turn determines the incidence of lung cancer. Several studies have investigated the relationship between CYP2A6 genotypes and lung cancer; however, the results are controversial. In this meta-analysis, we searched for all studies on the association between CYP2A6 genotypes and lung cancer indexed in the MEDLINE, PubMed, Embase, China Biological Medicine, and Wanfang databases from January 1, 1966 to August 1, 2011. The pooled odds ratios (ORs) for one CYP2A6 mutant allele and two CYP2A6 mutant alleles, in comparison with the wild-type CYP2A6 gene, were 0.82 [95% confidence interval (CI) = 0.73-0.92] and 0.57 (95% CI = 0.48-0.68), respectively. Furthermore, in two studies of participants who were all smokers, the associations of one CYP2A6 mutant allele and two CYP2A6 mutant alleles with reduced risk of lung cancer were strengthened, and the pooled ORs were 0.71 (95% CI = 0.58-0.87) and 0.47 (95% CI = 0.35-0.62), respectively. However, we did not find statistically significant relationships between CYP2A6 genotypes and lung cancer in studies that included both never smokers and smokers (pooled OR(one CYP2A6 mutant allele) = 0.88, 95% CI = 0.76-1.01; pooled OR(two CYP2A6 mutant alleles) = 0.61, 95% CI = 0.35-1.06). The results of this meta-analysis suggest that the reduced-activity CYP2A6 genotype may decrease the risk of lung cancer in smokers only. 23203414 20 26 CYP2A6 Gene 1548 23203414 53 64 lung cancer Disease D008175 23203414 0 19 Cytochrome P450 2A6 Gene 1548 23203414 21 27 CYP2A6 Gene 1548 23203414 149 155 CYP2A6 Gene 1548 23203414 215 221 CYP2A6 Gene 1548 23203414 376 387 lung cancer Disease D008175 23203414 448 454 CYP2A6 Gene 1548 23203414 469 480 lung cancer Disease D008175 23203414 600 606 CYP2A6 Gene 1548 23203414 621 632 lung cancer Disease D008175 23203414 799 805 CYP2A6 Gene 1548 23203414 828 834 CYP2A6 Gene 1548 23203414 884 890 CYP2A6 Gene 1548 23203414 1048 1059 all smokers Environment 1548-D008175 23203414 1085 1091 CYP2A6 Gene 1548 23203414 1114 1120 CYP2A6 Gene 1548 23203414 1157 1168 lung cancer Disease D008175 23203414 1356 1362 CYP2A6 Gene 1548 23203414 1377 1388 lung cancer Disease D008175 23203414 1460 1466 CYP2A6 Gene 1548 23203414 1524 1530 CYP2A6 Gene 1548 23203414 1644 1650 CYP2A6 Gene 1548 23203414 1685 1696 lung cancer Disease D008175 23203414 1700 1707 smokers Environment 1548-D008175 20044645|t|Significant association of DNA repair gene Ku80 genotypes with breast cancer susceptibility in Taiwan. 20044645|t|AIM: To evaluate the association between the genotypes of the heterodimeric DNA-binding component, Ku80 gene and the breast cancer risk in Taiwan. PATIENTS AND METHODS: In this hospital-based case-control study, the association of Ku80 G-1401T rs828907, Ku80 C-319T rs11685387 and Ku80 intron19 rs9288518 polymorphisms with breast cancer risk in a Taiwanese population was investigated. In total, 1272 patients with breast cancer and the same number of age- and gender-matched healthy controls were genotyped. RESULTS: A significantly different distribution was found in the frequency of the Ku80 G-1401T genotype, but not the Ku80 C-319T or intron 19 genotypes, between the breast cancer and control groups. The T allele Ku80 G-1401T conferred a significant (p=0.0069) increased risk of breast cancer. Gene interactions with smoking, but not with breastfeeding, were significant for the Ku80 G-1401T polymorphism. The Ku80 G-1401T GT and TT genotypes in association with smoking conferred an increased risk of 3.162 (95% confidence interval=2.275-4.393) for breast cancer. CONCLUSION: The T allele of Ku80 G-1401T may be associated with the development of breast cancer and may be a novel useful marker for breast cancer detection and prediction. 20044645 43 47 Ku80 Gene 7520 20044645 63 76 breast cancer Disease D001943 20044645 99 103 Ku80 Gene 7520 20044645 117 130 breast cancer Disease D001943 20044645 231 235 Ku80 Gene 7520 20044645 254 258 Ku80 Gene 7520 20044645 281 285 Ku80 Gene 7520 20044645 324 337 breast cancer Disease D001943 20044645 416 429 breast cancer Disease D001943 20044645 592 596 Ku80 Gene 7520 20044645 627 631 Ku80 Gene 7520 20044645 675 688 breast cancer Disease D001943 20044645 722 726 Ku80 Gene 7520 20044645 788 801 breast cancer Disease D001943 20044645 826 833 smoking Environment 7520-D001943 20044645 888 892 Ku80 Gene 7520 20044645 919 923 Ku80 Gene 7520 20044645 972 979 smoking Environment 7520-D001943 20044645 1059 1072 breast cancer Disease D001943 20044645 1102 1106 Ku80 Gene 7520 20044645 1157 1170 breast cancer Disease D001943 20044645 1208 1221 breast cancer Disease D001943 16175316|t|Modifying effects of sulfotransferase 1A1 gene polymorphism on the association of breast cancer risk with body mass index or endogenous steroid hormones. 16175316|t|Sulfotransferase (SULT) 1A1 is involved in the inactivation and elimination of estrogens and catechol estrogens. A common functional polymorphism (Arg213His) has been linked in our previous study of postmenopausal Caucasian women to an elevated risk of breast cancer and the association appeared to be modified by factors related to high endogenous estrogen exposures. We further evaluated this polymorphism and levels of BMI and steroid hormones in association with breast cancer risk in a population-based case-control study of Chinese women, involving 1102 incident cases aged 25-64 years and 1147 age-matched population controls. The SULT1A1 genotype was not associated with overall breast cancer risk in this population. A possible association was suggested for postmenopausal breast cancer (adjusted odds ratio [OR] = 1.4, 95% CI = 0.9-2.1 for subject carrying the variant His allele). The SULT1A1 genotype was found to significantly modify postmenopausal breast cancer risk associated with a high BMI (>or=25 kg/m2) (p for interaction = 0.02), with an adjusted OR of 3.6 (95% CI = 1.5-8.7) for women with the Arg/His genotype compared with 1.1 (0.8-1.5) for women with the Arg/Arg genotype (no His/His genotype was identified in this study population). Similarly, the risk associated with a long duration (>or=30 years) of menstruation also substantially differed by the SULT1A1 genotype (p for interaction = 0.05), with an OR of 4.0 (95% CI = 1.3-12.8) for women with the Arg/His genotype and 1.4 (0.8-2.5) for women with the Arg/Arg genotype. Positive associations with blood levels of steroid hormones were also found generally to be more pronounced among women carrying the His allele. No similar effect modification was found for premenopausal breast cancer, however. These data suggest that the SULT1A1 Arg213His polymorphism may modify the effect of endogenous sex hormone exposures on postmenopausal breast cancer risk. 16175316 82 95 breast cancer Disease D001943 16175316 106 121 body mass index Environment 6817-D001943 16175316 125 152 endogenous steroid hormones Environment 6817-D001943 16175316 0 27 Sulfotransferase (SULT) 1A1 Gene 6817 16175316 253 266 breast cancer Disease D001943 16175316 467 480 breast cancer Disease D001943 16175316 638 645 SULT1A1 Gene 6817 16175316 687 700 breast cancer Disease D001943 16175316 782 795 breast cancer Disease D001943 16175316 896 903 SULT1A1 Gene 6817 16175316 962 975 breast cancer Disease D001943 16175316 997 1022 a high BMI (>or=25 kg/m2) Environment 6817-D001943 16175316 1296 1342 a long duration (>or=30 years) of menstruation Environment 6817-D001943 16175316 1378 1385 SULT1A1 Gene 6817 16175316 1579 1611 blood levels of steroid hormones Environment 6817-D001943 16175316 1756 1769 breast cancer Disease D001943 16175316 1808 1815 SULT1A1 Gene 6817 16175316 1864 1896 endogenous sex hormone exposures Environment 6817-D001943 16175316 1915 1928 breast cancer Disease D001943 16982738|t|Implications of gene-environment interaction in studies of gene variants in breast cancer: an example of dietary isoflavones and the D356N polymorphism in the sex hormone-binding globulin gene. 16982738|t|Studies to identify common genetic variants contributing to breast cancer risk often yield inconsistent results. Breast cancer is a complex disease involving both genetic and environmental determinants. Dietary isoflavones are thought to reduce breast cancer risk by stimulating circulating sex hormone-binding globulin (SHBG) levels. The SHBG gene contains a D356N polymorphism and the N variant is associated with reduced SHBG clearance compared with the D variant. In this study, we show a significant gene-environment interaction between SHBG D356N polymorphism and dietary isoflavone exposure on circulating SHBG levels in 1,988 postmenopausal women. SHBG levels were positively associated with isoflavones in women carrying the N variant (etap2 = 1.9%; P = 0.006) but not in women carrying only the D variant (etap2 = 0.0%; P = 0.999; P(interaction) = 0.019). This finding shows that the subtle effects of some genetic variants may be magnified and only become detectable in the presence of certain exposures. This gene-environment interaction might explain heterogeneity in studies associating SHBG gene variants and soy consumption with breast cancer risk in Far East population exposed to high isoflavone levels compared with populations with lower levels. 16982738 76 89 breast cancer Disease D001943 16982738 105 124 dietary isoflavones Environment 6462-D001943 16982738 159 187 sex hormone-binding globulin Gene 6462 16982738 60 73 breast cancer Disease D001943 16982738 113 126 Breast cancer Disease D001943 16982738 245 258 breast cancer Disease D001943 16982738 291 319 sex hormone-binding globulin Gene 6462 16982738 321 325 SHBG Gene 6462 16982738 339 343 SHBG Gene 6462 16982738 424 428 SHBG Gene 6462 16982738 542 546 SHBG Gene 6462 16982738 570 597 dietary isoflavone exposure Environment 6462-D001943 16982738 613 617 SHBG Gene 6462 16982738 656 660 SHBG Gene 6462 16982738 1101 1105 SHBG Gene 6462 16982738 1124 1139 soy consumption Environment 6462-D001943 16982738 1145 1158 breast cancer Disease D001943 16982738 1198 1220 high isoflavone levels Environment 6462-D001943 16652158|t|A novel T-77C polymorphism in DNA repair gene XRCC1 contributes to diminished promoter activity and increased risk of non-small cell lung cancer. 16652158|t|X-ray repair cross-complementing 1 (XRCC1) plays a key role in DNA base excision repair and cells lacking its activity are hypersensitive to DNA damage. Recently, we reported a SNP (rs3213245, -77T>C) in the XRCC1 gene 5' untranslated region (UTR) was significantly associated with the risk of developing esophageal squamous-cell carcinoma. Computer analysis predicted that this SNP was in the core of Sp1-binding motif, which suggested its functional significance. Gel shift and super shift assays confirmed that -77T>C polymorphic site in the XRCC1 promoter was within the Sp1-binding motif and the T>C substitution greatly enhanced the binding affinity of Sp1 to this region. Luciferase assays indicated that the Sp1-high-affinity C-allelic XRCC1 promoter was associated with a reduced transcriptional activity. The association between -77T>C and three other amino-acid substitution-causing polymorphisms in XRCC1 and risk of lung cancer was examined in 1024 patients and 1118 controls and the results showed that only the -77T>C polymorphism was significantly associated with an increased risk of developing lung cancer. Multivariate logistic regression analysis found that an increased risk of lung cancer was associated with the variant XRCC1 -77 genotypes (TC and CC) compared with the TT genotype (OR=1.46, 95% CI=1.18-1.82; P=0.001) and the increased risk was more pronounced in smokers (OR=1.63, 95% CI=1.20-2.21) than in non-smokers (OR=1.28, 95% CI=0.94-1.76). Taken together, these results showed that the functional SNP -77T>C in XRCC1 5'UTR was associated with cancer development owing to the decreased transcriptional activity of C-allele-containing promoter with higher affinity to Sp1 binding. 16652158 46 51 XRCC1 Gene 7515 16652158 118 144 non-small cell lung cancer Disease D002289 16652158 0 34 X-ray repair cross-complementing 1 Gene 7515 16652158 36 41 XRCC1 Gene 7515 16652158 208 213 XRCC1 Gene 7515 16652158 330 339 carcinoma Disease D002277 16652158 402 405 Sp1 Gene 6667 16652158 545 550 XRCC1 Gene 7515 16652158 575 578 Sp1 Gene 6667 16652158 659 662 Sp1 Gene 6667 16652158 716 719 Sp1 Gene 6667 16652158 744 749 XRCC1 Gene 7515 16652158 911 916 XRCC1 Gene 7515 16652158 929 940 lung cancer Disease D008175 16652158 1112 1123 lung cancer Disease D008175 16652158 1199 1210 lung cancer Disease D008175 16652158 1243 1248 XRCC1 Gene 7515 16652158 1388 1395 smokers Environment 7515-D008175 16652158 1544 1549 XRCC1 Gene 7515 16652158 1576 1582 cancer Disease D009369 16652158 1699 1702 Sp1 Gene 6667 23430226|t|Confirmation of the reduction of hormone replacement therapy-related breast cancer risk for carriers of the HSD17B1_937_G variant. 23430226|t|17beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) plays an important role in the biosynthesis of 17beta-estradiol. The current study aimed at confirming the reduced risk of breast cancer in carriers of the non-synonymous HSD17B1_937_A>G (rs605059) polymorphism who used any hormone replacement therapy (HRT) for 10 years or longer. We performed an independent association study using four breast cancer case-control studies from Australia, Germany, and Sweden. In all, 5,777 cases and 8,189 age-matched controls of European descent were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and TaqMan. Risk estimates were calculated by interaction analysis and main effect analysis adjusted for age and study. Main effect analyses for women using any HRT for 10 years or longer (1,428 cases versus 1,724 controls) revealed a protective effect of the HSD17B1_937_G allele on breast cancer risk (OR 0.86, 95 % CI: 0.73-0.99; p = 0.048). Thus, our previous finding of a protective effect of the HSD17B1_937_G allele on HRT-associated breast cancer risk has now been confirmed both in independent large patient cohorts and a comprehensive pooled analysis supporting the hypothesis that a HSD17B1-mediated decreased conversion of estrone to the more potent 17beta-estradiol may reduce the estrogenic effects, thereby reducing the risk of developing breast cancer during long-term HRT use. 23430226 33 60 hormone replacement therapy Environment 3292-D001943 23430226 69 82 breast cancer Disease D001943 23430226 108 115 HSD17B1 Gene 3292 23430226 0 42 17beta-hydroxysteroid dehydrogenase type 1 Gene 3292 23430226 44 51 HSD17B1 Gene 3292 23430226 176 189 breast cancer Disease D001943 23430226 224 231 HSD17B1 Gene 3292 23430226 392 405 breast cancer Disease D001943 23430226 803 833 any HRT for 10 years or longer Environment 3292-D001943 23430226 906 911 HSD17 Gene 3292 23430226 930 943 breast cancer Disease D001943 23430226 1048 1055 HSD17B1 Gene 3292 23430226 1087 1100 breast cancer Disease D001943 23430226 1240 1247 HSD17B1 Gene 3292 23430226 1400 1413 breast cancer Disease D001943 23430226 1421 1438 long-term HRT use Environment 3292-D001943 27207565|t|Toxoplasma gondii exposure may modulate the influence of TLR2 genetic variation on bipolar disorder: a gene-environment interaction study. 27207565|t|BACKGROUND: Genetic vulnerability to environmental stressors is yet to be clarified in bipolar disorder (BD), a complex multisystem disorder in which immune dysfunction and infectious insults seem to play a major role in the pathophysiology. Association between pattern-recognition receptor coding genes and BD had been previously reported. However, potential interactions with history of pathogen exposure are yet to be explored. METHODS: 138 BD patients and 167 healthy controls were tested for serostatus of Toxoplasma gondii, CMV, HSV-1 and HSV-2 and genotyped for TLR2 (rs4696480 and rs3804099), TLR4 (rs1927914 and rs11536891) and NOD2 (rs2066842) polymorphisms (SNPs). Both the pathogen-specific seroprevalence and the TLR/NOD2 genetic profiles were compared between patients and controls followed by modelling of interactions between these genes and environmental infectious factors in a regression analysis. RESULTS: First, here again we observed an association between BD and Toxoplasma gondii (p = 0.045; OR = 1.77; 95 % CI 1.01-3.10) extending the previously published data on a cohort of a relatively small number of patients (also included in the present sample). Second, we found a trend for an interaction between the TLR2 rs3804099 SNP and Toxoplasma gondii seropositivity in conferring BD risk (p = 0.017, uncorrected). CONCLUSIONS: Pathogen exposure may modulate the influence of the immunogenetic background on BD. A much larger sample size and information on period of pathogen exposure are needed in future gene-environment interaction studies. 27207565 0 26 Toxoplasma gondii exposure Environment 7097-D001714 27207565 57 61 TLR2 Gene 7097 27207565 83 99 bipolar disorder Disease D001714 27207565 87 103 bipolar disorder Disease D001714 27207565 105 107 BD Disease D001714 27207565 120 140 multisystem disorder Disease 1 27207565 308 310 BD Disease D001714 27207565 444 446 BD Disease D001714 27207565 569 573 TLR2 Gene 7097 27207565 601 605 TLR4 Gene 7099 27207565 637 641 NOD2 Gene 64127 27207565 730 734 NOD2 Gene 64127 27207565 979 981 BD Disease D001714 27207565 1234 1238 TLR2 Gene 7097 27207565 1257 1289 Toxoplasma gondii seropositivity Environment 7097-D001714 27207565 1304 1306 BD Disease D001714 27207565 1351 1368 Pathogen exposure Environment 7097-D001714 27207565 1431 1433 BD Disease D001714 14501269|t|Smoking and the risk of lung cancer: susceptibility with GSTP1 polymorphisms. 14501269|t|BACKGROUND: GSTP1 is a gene that helps detoxify foreign substances in the body. Functional polymorphisms of GSTP1 have been studied as risk factors for lung cancer. Past studies have compared the effect of the "at risk" polymorphism in two strata of smoking pack-years (usually defined by the median among controls). We examined the interaction between GSTP1 polymorphisms and cumulative exposure to smoking and their association with lung cancer risk. METHODS: Data are from a large hospital-based case-control study of persons treated for primary lung cancer at the Massachusetts General Hospital since 1992. Controls were drawn from friends and nonrelated family members. We genotyped 1,042 cases and 1,161 controls for GSTP1 using polymerase chain reaction-restriction fragment length polymorphism techniques. FINDINGS: The GSTP1 GG genotype approximately doubled the lung cancer risk associated with pack-years. This interaction was stronger among current smokers. At 26 pack-years (median among controls with a smoking history), the adjusted odds ratio for the association between pack-years and lung cancer risk was 13 (95% confidence interval = 6.5-25) among current smokers with the GSTP1 GG genotype compared with 6.1 (95% confidence interval = 4.9-7.5) among those with the GSTP1 AA genotype. CONCLUSIONS: GSTP1 GG increases the lung cancer risk associated with pack-years of smoking. 14501269 24 35 lung cancer Disease D008175 14501269 57 62 GSTP1 Gene 2950 14501269 12 17 GSTP1 Gene 2950 14501269 108 113 GSTP1 Gene 2950 14501269 152 163 lung cancer Disease D008175 14501269 353 358 GSTP1 Gene 2950 14501269 435 446 lung cancer Disease D008175 14501269 549 560 lung cancer Disease D008175 14501269 723 728 GSTP1 Gene 2950 14501269 828 833 GSTP1 Gene 2950 14501269 872 883 lung cancer Disease D008175 14501269 905 915 pack-years Environment 2950-D008175 14501269 953 968 current smokers Environment 2950-D008175 14501269 973 986 26 pack-years Environment 2950-D008175 14501269 988 1032 median among controls with a smoking history Environment 2950-D008175 14501269 1087 1097 pack-years Environment 2950-D008175 14501269 1102 1113 lung cancer Disease D008175 14501269 1167 1182 current smokers Environment 2950-D008175 14501269 1192 1197 GSTP1 Gene 2950 14501269 1285 1290 GSTP1 Gene 2950 14501269 1317 1322 GSTP1 Gene 2950 14501269 1340 1351 lung cancer Disease D008175 14501269 1373 1394 pack-years of smoking Environment 2950-D008175 18349090|t|Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. 18349090|t|CONTEXT: In addition to trauma exposure, other factors contribute to risk for development of posttraumatic stress disorder (PTSD) in adulthood. Both genetic and environmental factors are contributory, with child abuse providing significant risk liability. OBJECTIVE: To increase understanding of genetic and environmental risk factors as well as their interaction in the development of PTSD by gene x environment interactions of child abuse, level of non-child abuse trauma exposure, and genetic polymorphisms at the stress-related gene FKBP5. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study examining genetic and psychological risk factors in 900 nonpsychiatric clinic patients (762 included for all genotype studies) with significant levels of childhood abuse as well as non-child abuse trauma using a verbally presented survey combined with single-nucleotide polymorphism (SNP) genotyping. Participants were primarily urban, low-income, black (>95%) men and women seeking care in the general medical care and obstetrics-gynecology clinics of an urban public hospital in Atlanta, Georgia, between 2005 and 2007. MAIN OUTCOME MEASURES: Severity of adult PTSD symptomatology, measured with the modified PTSD Symptom Scale, non-child abuse (primarily adult) trauma exposure and child abuse measured using the traumatic events inventory and 8 SNPs spanning the FKBP5 locus. RESULTS: Level of child abuse and non-child abuse trauma each separately predicted level of adult PTSD symptomatology (mean [SD], PTSD Symptom Scale for no child abuse, 8.03 [10.48] vs > or =2 types of abuse, 20.93 [14.32]; and for no non-child abuse trauma, 3.58 [6.27] vs > or =4 types, 16.74 [12.90]; P < .001). Although FKBP5 SNPs did not directly predict PTSD symptom outcome or interact with level of non-child abuse trauma to predict PTSD symptom severity, 4 SNPs in the FKBP5 locus significantly interacted (rs9296158, rs3800373, rs1360780, and rs9470080; minimum P = .0004) with the severity of child abuse to predict level of adult PTSD symptoms after correcting for multiple testing. This gene x environment interaction remained significant when controlling for depression severity scores, age, sex, levels of non-child abuse trauma exposure, and genetic ancestry. This genetic interaction was also paralleled by FKBP5 genotype-dependent and PTSD-dependent effects on glucocorticoid receptor sensitivity, measured by the dexamethasone suppression test. CONCLUSIONS: Four SNPs of the FKBP5 gene interacted with severity of child abuse as a predictor of adult PTSD symptoms. There were no main effects of the SNPs on PTSD symptoms and no significant genetic interactions with level of non-child abuse trauma as predictor of adult PTSD symptoms, suggesting a potential gene-childhood environment interaction for adult PTSD. 18349090 15 20 FKBP5 Gene 2289 18349090 39 54 childhood abuse Environment 2289-D013313 18349090 68 97 posttraumatic stress disorder Disease D013313 18349090 24 30 trauma Disease D014947 18349090 93 122 posttraumatic stress disorder Disease D013313 18349090 124 128 PTSD Disease D013313 18349090 386 390 PTSD Disease D013313 18349090 467 473 trauma Disease D014947 18349090 537 542 FKBP5 Gene 2289 18349090 800 806 trauma Disease D014947 18349090 1166 1170 PTSD Disease D013313 18349090 1214 1218 PTSD Disease D013313 18349090 1268 1274 trauma Disease D014947 18349090 1319 1328 traumatic Disease D014947 18349090 1370 1375 FKBP5 Gene 2289 18349090 1433 1439 trauma Disease D014947 18349090 1481 1485 PTSD Disease D013313 18349090 1513 1517 PTSD Disease D013313 18349090 1634 1640 trauma Disease D014947 18349090 1707 1712 FKBP5 Gene 2289 18349090 1743 1747 PTSD Disease D013313 18349090 1806 1812 trauma Disease D014947 18349090 1824 1828 PTSD Disease D013313 18349090 1861 1866 FKBP5 Gene 2289 18349090 1971 1998 the severity of child abuse Environment 2289-D013313 18349090 2025 2029 PTSD Disease D013313 18349090 2156 2166 depression Disease D003866 18349090 2220 2226 trauma Disease D014947 18349090 2307 2312 FKBP5 Gene 2289 18349090 2336 2340 PTSD Disease D013313 18349090 2477 2482 FKBP5 Gene 2289 18349090 2504 2527 severity of child abuse Environment 2289-D013313 18349090 2552 2556 PTSD Disease D013313 18349090 2609 2613 PTSD Disease D013313 18349090 2693 2699 trauma Disease D014947 18349090 2722 2726 PTSD Disease D013313 18349090 2765 2786 childhood environment Environment 2289-D013313 18349090 2809 2813 PTSD Disease D013313 18162478|t|Meta- and pooled analyses of the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer risk: a huge-GSEC review. 18162478|t|Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate, whose role in gastric carcinogenesis is controversial. The authors performed a meta-analysis and individual data pooled analysis of case-control studies that examined the association between C677T and A1298C polymorphisms (the former being associated with low folate serum levels) and gastric cancer (meta-analyses: 16 studies, 2,727 cases and 4,640 controls for C677T and seven studies, 1,223 cases and 2,015 controls for A1298C; pooled analyses: nine studies, 1,540 cases and 2,577 controls for C677T and five studies, 1,146 cases and 1,549 controls for A1298C). An increased risk was found for MTHFR 677 TT in the meta-analysis (odds ratio (OR) = 1.52, 95% confidence interval (CI): 1.31, 1.77) and pooled analysis (OR = 1.49, 95% CI: 1.14, 1.95). No association resulted for MTHFR 1298 CC (meta-OR = 0.94, 95% CI: 0.65, 1.35; pooled OR = 0.90, 95% CI: 0.69, 1.34). Results from the pooled analysis of four studies on C677T stratified according to folate levels showed an increased risk for individuals with low (OR = 2.05, 95% CI: 1.13, 3.72) versus high (OR = 0.95, 95% CI: 0.54, 1.67) folate levels. Overall, these findings support the hypothesis that folate plays a role in gastric carcinogenesis. 18162478 33 68 methylenetetrahydrofolate reductase Gene 4524 18162478 104 118 gastric cancer Disease D013274 18162478 0 35 Methylenetetrahydrofolate reductase Gene 4524 18162478 37 42 MTHFR Gene 4524 18162478 111 125 carcinogenesis Disease D063646 18162478 374 388 gastric cancer Disease D013274 18162478 686 691 MTHFR Gene 4524 18162478 868 873 MTHFR Gene 4524 18162478 1180 1193 folate levels Environment 4524-D013274 18162478 1247 1253 folate Environment 4524-D013274 18162478 1278 1292 carcinogenesis Disease D063646 19178978|t|A meta-analysis of TP53 codon 72 polymorphism and lung cancer risk: evidence from 15,857 subjects. 19178978|t|The genetic polymorphism of TP53 codon 72 is thought to have significant effect on lung cancer risk, but the results are inconsistent. In this meta-analysis, we assessed 23 published studies involving 15,857 subjects of the association between TP53 codon 72 polymorphism and risk of lung cancer. For the homozygote Pro/Pro and Pro allele carriers (Pro/Pro+Pro/Arg), the ORs for all studies combined (7495 cases and 8362 controls) were 1.221 (95% CI=1.046-1.425; P=0.021 for heterogeneity) and 1.148 (95% CI=1.040-1.266; P=0.008 for heterogeneity). In the stratified analysis by ethnicity, significantly increased risks were found in Asians (3254 cases and 3350 controls) for both the homozygote Pro/Pro (OR=1.395; 95% CI=1.206-1.613; P=0.806 for heterogeneity) and the Pro allele carriers (OR=1.109; 95% CI=1.000-1.228; P=0.458 for heterogeneity). In Caucasians (3359 cases and 3953 controls), significantly elevated risk was associated with Pro allele carriers (OR=1.180; 95% CI=1.029-1.353; P=0.073 for heterogeneity). In the subgroup analyses by pathological type, the ORs for the homozygote Pro/Pro and Pro allele carriers were 1.289 (95% CI=1.027-1.618; P=0.096 for heterogeneity) and 1.168 (95% CI=1.062-1.284; P=0.231 for heterogeneity) for lung adenocarcinoma (2724 cases and 6591 controls). When stratified by smoking status, the pooled OR was 1.440 (95% CI=1.078-1.923; P=0.042 for heterogeneity) for the Pro allele carriers among smokers (1480 cases and 1414 controls). Although some statistical bias could not be eliminated, this meta-analysis suggests that the Pro allele is a low-penetrant risk factor for developing lung cancer. Additionally, we found that this phenomenon was more prominent in subgroups such as in Asians and Caucasians, in lung adenocarcinoma, or in smokers. 19178978 19 23 TP53 Gene 7157 19178978 50 61 lung cancer Disease D008175 19178978 28 32 TP53 Gene 7157 19178978 83 94 lung cancer Disease D008175 19178978 244 248 TP53 Gene 7157 19178978 283 294 lung cancer Disease D008175 19178978 633 639 Asians Environment 7157-D008175 19178978 851 861 Caucasians Environment 7157-D008175 19178978 1248 1267 lung adenocarcinoma Disease C538231 19178978 1248 1267 lung adenocarcinoma Environment 7157-D008175 19178978 1441 1448 smokers Environment 7157-D008175 19178978 1631 1642 lung cancer Disease D008175 19178978 1731 1737 Asians Environment 7157-D008175 19178978 1742 1752 Caucasians Environment 7157-D008175 19178978 1757 1776 lung adenocarcinoma Disease C538231 19178978 1757 1776 lung adenocarcinoma Environment 7157-D008175 19178978 1784 1791 smokers Environment 7157-D008175 21178102|t|Polymorphisms in inflammatory response genes and their association with gastric cancer: A HuGE systematic review and meta-analyses. 21178102|t|To evaluate the association between gastric cancer susceptibility and inflammation-related gene polymorphisms, the authors conducted a series of meta-analyses using a predefined protocol. Genes investigated were those coding for the interleukin (IL) proteins (IL1B, IL1RN, IL8, and IL10) and for tumor necrosis factor-alpha. Gastric cancers were stratified by histologic subtype and anatomic subsite, by Helicobacter pylori infection status, by geographic location (Asian or non-Asian study population), and by a quantitative index of study quality. All published literature and meeting abstracts from the period 1990-2006 were considered. Results consistently supported increased cancer risk for IL1RN2 carriers; the increased risk was specific to non-Asian populations and was seen for intestinal and diffuse cancers, distal cancers, and, to a lesser extent, cardia cancers. Analyses restricted to high-quality studies or H. pylori-positive cases and controls also showed significant associations with both carrier status and homozygosity status. In Asian populations, reduced risk was observed in association with IL1B-31C carrier status. This effect was also observed in analyses restricted to high-quality studies. These results indicate the importance of stratification by anatomic site, histologic type, H. pylori infection, and country of origin. Study quality considerations, both laboratory and epidemiologic, can also affect results and may explain, in part, the variability in results published to date. 21178102 72 86 gastric cancer Disease D013274 21178102 36 50 gastric cancer Disease D013274 21178102 70 82 inflammation Disease D007249 21178102 260 264 IL1B Gene 3553 21178102 266 271 IL1RN Gene 3557 21178102 273 276 IL8 Gene 3576 21178102 282 286 IL10 Gene 3586 21178102 296 323 tumor necrosis factor-alpha Gene 7124 21178102 302 310 necrosis Disease D009336 21178102 325 340 Gastric cancers Disease D013274 21178102 424 433 infection Disease D007239 21178102 681 687 cancer Disease D009369 21178102 749 770 non-Asian populations Environment 3557-D013274 21178102 788 818 intestinal and diffuse cancers Environment 3557-D013274 21178102 811 818 cancers Disease D009369 21178102 820 834 distal cancers Environment 3557-D013274 21178102 827 834 cancers Disease D009369 21178102 861 875 cardia cancers Environment 3557-D013274 21178102 868 875 cancers Disease D009369 21178102 1052 1069 Asian populations Environment 3557-D013274 21178102 1117 1121 IL1B Gene 3553 21178102 1279 1292 anatomic site Environment 3557-D013274 21178102 1294 1330 histologic type, H. pylori infection Environment 3557-D013274 21178102 1321 1330 infection Disease D007239 21178102 1336 1353 country of origin Environment 3557-D013274 17051426|t|Genetic variation in IGF1, IGFBP3, IRS1, IRS2 and risk of breast cancer in women living in Southwestern United States. 17051426|t|BACKGROUND: An insulin-related pathway to breast cancer has been hypothesized. METHODS: We examine the 19 CA repeat of the IGF1 gene, the -202 C > A IGFBP3, the G972R IRS, and the G1057D IRS2 polymorphisms among 1,175 non-Hispanic white (NHW) and 576 Hispanic newly diagnosed breast cancer cases and 1,330 NHW and 727 Hispanic controls living in Arizona, Colorado, New Mexico, and Utah. RESULTS: Among post-menopausal women not recently exposed to hormones, not having the 19 CA repeat of IGF1 gene was associated with breast cancer among NHW women [odds ratio (OR) 2.14, 95% confidence interval (CI) 1.21-3.79] and having an R allele of G972R IRS1 increased breast cancer risk among Hispanic women (OR 2.70, 95% CI 1.13-6.46). Among post-menopausal Hispanic women recently exposed to hormones the A allele of the -202 C > A IGFBP3 polymorphism increased risk of breast cancer (OR 1.57, 95% CI 1.06-2.33). The IGF1 19 CA repeat polymorphism interacted with hormone replacement therapy (HRT) among NHW post-menopausal women; women who had the 19/19 IGF1 genotype were at reduced risk of breast cancer (OR 0.64, 95% CI 0.47-0.88) if they did not use HRT. We also observed interaction between body mass index and IGF1 19 CA repeat (p=0.06) and between weight gain and the -202 C > A IGFBP3 polymorphism (p=0.05) in NHW post-menopausal women not recently exposed to hormones. CONCLUSIONS: Our data suggest that associations between insulin-related genes and breast cancer risk among women living in the Southwestern United States may be dependent on estrogen exposure and may differ by ethnicity. 17051426 21 25 IGF1 Gene 3479 17051426 27 33 IGFBP3 Gene 3486 17051426 35 39 IRS1 Gene 3667 17051426 41 45 IRS2 Gene 8660 17051426 58 71 breast cancer Disease D001943 17051426 15 22 insulin Gene 3630 17051426 42 55 breast cancer Disease D001943 17051426 123 127 IGF1 Gene 3479 17051426 149 155 IGFBP3 Gene 3486 17051426 187 191 IRS2 Gene 8660 17051426 276 289 breast cancer Disease D001943 17051426 489 493 IGF1 Gene 3479 17051426 519 532 breast cancer Disease D001943 17051426 644 648 IRS1 Gene 3667 17051426 659 672 breast cancer Disease D001943 17051426 684 698 Hispanic women Environment 3667-D001943 17051426 734 793 post-menopausal Hispanic women recently exposed to hormones Environment 3486-D001943 17051426 825 831 IGFBP3 Gene 3486 17051426 863 876 breast cancer Disease D001943 17051426 910 914 IGF1 Gene 3479 17051426 957 984 hormone replacement therapy Environment 3479-D001943 17051426 986 989 HRT Environment 3479-D001943 17051426 1048 1052 IGF1 Gene 3479 17051426 1086 1099 breast cancer Disease D001943 17051426 1131 1151 they did not use HRT Environment 3479-D001943 17051426 1190 1205 body mass index Environment 3479-D001943 17051426 1210 1214 IGF1 Gene 3479 17051426 1249 1260 weight gain Disease D015430 17051426 1249 1260 weight gain Environment 3479-D001943 17051426 1280 1286 IGFBP3 Gene 3486 17051426 1428 1435 insulin Gene 3630 17051426 1454 1467 breast cancer Disease D001943 17051426 1546 1563 estrogen exposure Environment 3479-D001943 17051426 1546 1563 estrogen exposure Environment 3486-D001943 17051426 1582 1591 ethnicity Environment 3667-D001943 19811586|t|Chronic and acute stress, gender, and serotonin transporter gene-environment interactions predicting depression symptoms in youth. 19811586|t|BACKGROUND: Many recent studies of serotonin transporter gene by environment effects predicting depression have used stress assessments with undefined or poor psychometric methods, possibly contributing to wide variation in findings. The present study attempted to distinguish between effects of acute and chronic stress to predict depressive symptoms at age 20 among 346 youth varying in polymorphisms of the 5HTT gene who had been assessed at ages 15 and 20. METHODS: Interview measures assessed major acute life events between 15 and 19, and multiple interviews and questionnaires with youths and their parents at youth age 15 provided an index of chronic family stress. Lg alleles were reclassified as S. RESULTS: Chronic family stress at age 15 predicted higher depression scores at 20 among those with one or two S alleles, and the effects of genetic moderation were significant only for females. Gene-environment interactions with acute stress were nonsignificant. CONCLUSIONS: Careful measurement and separation of the effects of chronic and acute stress, and gender, are encouraged in the study of mechanisms of the stress-depression association. 19811586 38 59 serotonin transporter Gene 6532 19811586 101 111 depression Disease D003866 19811586 35 56 serotonin transporter Gene 6532 19811586 96 106 depression Disease D003866 19811586 332 351 depressive symptoms Disease D003866 19811586 410 414 5HTT Gene 6532 19811586 718 739 Chronic family stress Environment 6532-D003866 19811586 767 777 depression Disease D003866 19811586 894 901 females Environment 6532-D003866 19811586 1132 1142 depression Disease D003866 19671832|t|Interactive effect of cigarette smoking with human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) polymorphisms on the risk of lung cancer: a case-control study in Taiwan. 19671832|t|Human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) plays an important role in repairing oxidative DNA damage induced by tobacco carcinogens. In this case-control study, the authors examined the interactive effect of hOGG1 gene polymorphisms and cigarette smoking on the risk of lung cancer in Taiwan. A total of 1,096 cases and 1,007 controls were enrolled from 6 medical centers in Taiwan during 2002-2004. hOGG1 Ser326Cys genetic polymorphisms were determined using the MassARRAY system (SEQUENOM, Inc., San Diego, California). Tobacco smoking history was obtained through personal interview according to a structured questionnaire. Logistic regression analysis was used to estimate multivariate-adjusted odds ratios and 95% confidence intervals. The odds of developing lung cancer for persons with the Cys/Cys genotype versus the Ser/Ser genotype were 1.11 (95% confidence interval (CI): 0.74, 1.65) for never smokers, 1.45 (95% CI: 0.74, 2.83) for moderate smokers, and 3.52 (95% CI: 1.54, 8.06) for heavy smokers. The P value for interaction in the logistic model was 0.01. The increased risk associated with the Cys/Cys genotype among heavy smokers remained statistically significant for various histologic types of lung cancer, including adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. The authors conclude that there was a noticeable modifying effect on the association between hOGG1 genotype and lung cancer risk by cigarette smoking status. 19671832 22 39 cigarette smoking Environment 4968-D008175 19671832 85 90 hOGG1 Gene 4968 19671832 121 132 lung cancer Disease D008175 19671832 40 45 hOGG1 Gene 4968 19671832 212 217 hOGG1 Gene 4968 19671832 274 285 lung cancer Disease D008175 19671832 404 409 hOGG1 Gene 4968 19671832 768 779 lung cancer Disease D008175 19671832 1000 1013 heavy smokers Environment 4968-D008175 19671832 1137 1150 heavy smokers Environment 4968-D008175 19671832 1218 1229 lung cancer Disease D008175 19671832 1241 1255 adenocarcinoma Disease D000230 19671832 1257 1280 squamous cell carcinoma Disease D002294 19671832 1286 1306 small cell carcinoma Disease D018288 19671832 1401 1406 hOGG1 Gene 4968 19671832 1420 1431 lung cancer Disease D008175 19671832 1440 1464 cigarette smoking status Environment 4968-D008175 17187234|t|ESR1, AR, body size, and breast cancer risk in Hispanic and non-Hispanic white women living in the Southwestern United States. 17187234|t|Estrogen and androgen are thought to influence breast cancer risk. The actions of estrogens and androgens are mediated through the respective receptors. In this study we examine the association of the Xb1 polymorphism of estrogen receptor alpha (ESR1) and the CAG repeat of the androgen receptor (AR) gene with risk of breast cancer in women living in the Southwestern United States. Cases (N = 1169 non-Hispanic white (NHW) and 576 Hispanic) with first primary breast cancer were matched to controls (N = 1330 NHW and 725 Hispanic) by location (Arizona, Colorado, New Mexico, or Utah) and 5-year age group. Detailed weight history was obtained along with other diet and lifestyle information. Neither the ESR1 nor the AR polymorphisms evaluated were associated independently with breast cancer risk in either Hispanic or NHW women. However, among Hispanic women taking hormone replacement therapy (HRT), there was a 40% reduced risk of breast cancer among women with an X allele (95% CI 0.39, 0.94). Also Hispanic women with the xx genotype had a significant reduced risk of breast cancer in the presence of weight gain prior to age 50 if post-menopausal or prior to diagnosis if pre-menopausal (P interaction 0.02 and <0.01 respectively). These results suggest differences in risk factors for NHW and Hispanic women. However, they provide only minor support for the role of the AR and ESR1 gene in the etiology of breast cancer. 17187234 0 4 ESR1 Gene 2099 17187234 6 8 AR Gene 367 17187234 25 38 breast cancer Disease D001943 17187234 47 60 breast cancer Disease D001943 17187234 246 250 ESR1 Gene 2099 17187234 278 295 androgen receptor Gene 367 17187234 297 299 AR Gene 367 17187234 319 332 breast cancer Disease D001943 17187234 462 475 breast cancer Disease D001943 17187234 706 710 ESR1 Gene 2099 17187234 719 721 AR Gene 367 17187234 781 794 breast cancer Disease D001943 17187234 863 903 taking hormone replacement therapy (HRT) Environment 2099-D001943 17187234 863 903 taking hormone replacement therapy (HRT) Environment 367-D001943 17187234 937 950 breast cancer Disease D001943 17187234 1076 1089 breast cancer Disease D001943 17187234 1109 1120 weight gain Disease D015430 17187234 1109 1136 weight gain prior to age 50 Environment 2099-D001943 17187234 1109 1136 weight gain prior to age 50 Environment 367-D001943 17187234 1380 1382 AR Gene 367 17187234 1387 1391 ESR1 Gene 2099 17187234 1416 1429 breast cancer Disease D001943 19168583|t|Nitric oxide synthase gene polymorphisms and prostate cancer risk. 19168583|t|Nitric oxide (NO) induces cytotoxicity and angiogenesis, and may play a role in prostate carcinogenesis, potentially modulated by environmental exposures. We evaluated the association of prostate cancer with genetic polymorphisms in two genes related to intracellular NO: NOS2A [inducible nitric oxide synthase (NOS); -2892T>C, Ex16 + 14C>T (S608L), IVS16 + 88T>G and IVS20 + 524G>A] and NOS3 [endothelial NOS; IVS1-762C>T, Ex7-43C>T (D258D), IVS7-26A>G, Ex8-63G>T (E298D) and IVS15-62G>T]. Prostate cancer cases (n = 1320) from the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial were frequency matched to controls (n = 1842), by age, race, time since initial screening and year of blood draw. An antioxidant score [range 3-12; low (3-7) versus high (8-12)] was created by summing the quartile levels of vitamin E, beta-carotene and lycopene, which were coded from 1 to 4, respectively. The global tests for all eight single-nucleotide polymorphisms (SNPs) (excluding NOS2A-2892T>C, with low minor allele frequency) were statistically significant for prostate cancer (P = 0.005), especially for aggressive cancer (stage III-IV or Gleason score > or = 7) (P = 0.01). The NOS2A IVS16 + 88 GT/TT was associated with increased prostate cancer risk (odds ratio = 1.24, 95% confidence interval = 1.00-1.54), whereas the IVS20 + 524 AG/GG was associated with decreased risk (0.77, 0.66-0.90). The NOS3 IVS7-26GG was associated with increased prostate cancer risk (1.33, 1.07-1.64). All these SNPs showed significant associations with aggressive cancer and not for non-aggressive cancer. In the evaluation of effect modification, the effect of the NOS2A IVS16 + 88 GT/TT on aggressive cancer was stronger among subjects with higher antioxidant intake (1.61, 1.18-2.19; P(interaction) = 0.01). Our results suggest that NOS gene polymorphisms are genetic susceptibility factors for aggressive prostate cancer. 19168583 0 21 Nitric oxide synthase Gene 4843 19168583 45 60 prostate cancer Disease D011471 19168583 26 38 cytotoxicity Disease D064420 19168583 89 103 carcinogenesis Disease D063646 19168583 187 202 prostate cancer Disease D011471 19168583 208 215 genetic Disease 1 19168583 272 277 NOS2A Gene 4843 19168583 289 310 nitric oxide synthase Gene 4843 19168583 312 315 NOS Gene 4843 19168583 388 392 NOS3 Gene 4846 19168583 406 409 NOS Gene 4843 19168583 491 506 Prostate cancer Disease D011471 19168583 570 580 Colorectal Disease D015179 19168583 585 599 Ovarian Cancer Disease D010051 19168583 1004 1009 NOS2A Gene 4843 19168583 1087 1102 prostate cancer Disease D011471 19168583 1142 1148 cancer Disease D009369 19168583 1206 1211 NOS2A Gene 4843 19168583 1259 1274 prostate cancer Disease D011471 19168583 1426 1430 NOS3 Gene 4846 19168583 1471 1486 prostate cancer Disease D011471 19168583 1574 1580 cancer Disease D009369 19168583 1608 1614 cancer Disease D009369 19168583 1676 1681 NOS2A Gene 4843 19168583 1713 1719 cancer Disease D009369 19168583 1753 1778 higher antioxidant intake Environment 4843-D011471 19168583 1846 1849 NOS Gene 4843 19168583 1873 1880 genetic Disease 1 19168583 1919 1934 prostate cancer Disease D011471 15734955|t|Polymorphisms in XRCC1 modify the association between polycyclic aromatic hydrocarbon-DNA adducts, cigarette smoking, dietary antioxidants, and breast cancer risk. 15734955|t|The variability in DNA repair capacity of the general population may depend in part upon common variants in DNA repair genes. X-ray repair cross complementing group 1 (XRCC1) is an important DNA base excision repair gene and exhibits polymorphic variation. Using the Long Island Breast Cancer Study Project, a population-based case-control study, we evaluated the hypothesis that two common single nucleotide polymorphisms of XRCC1 (codon 194 Arg-->Trp and 399 Arg-->Gln) influence breast cancer susceptibility and interact with polycyclic aromatic hydrocarbon (PAH)-DNA adducts, cigarette smoking, and intake of fruits and vegetables and antioxidants. The available sample for genotyping included 1,067 cases and 1,110 controls. Genotyping was done by a high-throughput single-nucleotide extension assay with fluorescence polarization detection of the incorporated nucleotide. We observed no significant increases in risk among all subjects who were carriers of XRCC1 194Trp or 399Gln alleles. Among never smokers, we observed an increased risk of breast cancer in 399Gln carriers [odds ratio (OR), 1.3; 95% confidence interval (CI), 1.0-1.7). Further analysis indicated a suggestive weak additive interaction between the 399Gln allele and detectable PAH-DNA adducts (OR for exposure with mutant genotype, 1.9; 95% CI, 1.2-3.1). The estimated age-adjusted interaction contrast ratio (ICR) and 95% CI (ICR, 0.38; 95% CI, -0.32 to 1.10) indicated that the departure from additivity was not statistically significant, but that there was some suggestion of a relative excess risk due to the interaction. In subjects with at least one copy of XRCC1 194Trp allele, there was a moderate interaction with high intake of fruits and vegetables (>/=35 half-cup servings per week of any fruits, fruit juices, and vegetables, OR, 0.58; 95% CI, 0.38-0.89; ICR, -0.49; 95% CI, -0.03 to -0.95), and dietary plus supplement antioxidant intake with 33% to 42% decreases in breast cancer risk compared with those with the Arg194Arg genotype and low-intake individuals. These results do not show that the two genetic polymorphisms of XRCC1 independently influence breast cancer risk. However, there is evidence for interactions between the two XRCC1 single nucleotide polymorphisms and PAH-DNA adducts or fruit and vegetable and antioxidant intake on breast cancer risk. Further understanding of the biological function of XRCC1 variants and their interactions with PAH-DNA adducts, antioxidants, and other genes in the pathway are needed. 15734955 17 22 XRCC1 Gene 7515 15734955 54 97 polycyclic aromatic hydrocarbon-DNA adducts Environment 7515-D001943 15734955 99 116 cigarette smoking Environment 7515-D001943 15734955 118 138 dietary antioxidants Environment 7515-D001943 15734955 144 157 breast cancer Disease D001943 15734955 126 166 X-ray repair cross complementing group 1 Gene 7515 15734955 168 173 XRCC1 Gene 7515 15734955 279 292 Breast Cancer Disease D001943 15734955 426 431 XRCC1 Gene 7515 15734955 482 495 breast cancer Disease D001943 15734955 963 968 XRCC1 Gene 7515 15734955 1001 1014 never smokers Environment 7515-D001943 15734955 1049 1062 breast cancer Disease D001943 15734955 1241 1267 detectable PAH-DNA adducts Environment 7515-D001943 15734955 1639 1644 XRCC1 Gene 7515 15734955 1698 1734 high intake of fruits and vegetables Environment 7515-D001943 15734955 1736 1812 >/=35 half-cup servings per week of any fruits, fruit juices, and vegetables Environment 7515-D001943 15734955 1884 1926 dietary plus supplement antioxidant intake Environment 7515-D001943 15734955 1956 1969 breast cancer Disease D001943 15734955 2115 2120 XRCC1 Gene 7515 15734955 2145 2158 breast cancer Disease D001943 15734955 2225 2230 XRCC1 Gene 7515 15734955 2267 2282 PAH-DNA adducts Environment 7515-D001943 15734955 2286 2305 fruit and vegetable Environment 7515-D001943 15734955 2310 2328 antioxidant intake Environment 7515-D001943 15734955 2332 2345 breast cancer Disease D001943 15734955 2404 2409 XRCC1 Gene 7515 18500343|t|Multiple ADH genes are associated with upper aerodigestive cancers. 18500343|t|Alcohol is an important risk factor for upper aerodigestive cancers and is principally metabolized by alcohol dehydrogenase (ADH) enzymes. We have investigated six ADH genetic variants in over 3,800 aerodigestive cancer cases and 5,200 controls from three individual studies. Gene variants rs1229984 (ADH1B) and rs1573496 (ADH7) were significantly protective against aerodigestive cancer in each individual study and overall (P = 10(-10) and 10(-9), respectively). These effects became more apparent with increasing alcohol consumption (P for trend = 0.0002 and 0.065, respectively). Both gene effects were independent of each other, implying that multiple ADH genes may be involved in upper aerodigestive cancer etiology. 18500343 9 12 ADH Gene 10327 18500343 59 66 cancers Disease D009369 18500343 60 67 cancers Disease D009369 18500343 102 123 alcohol dehydrogenase Gene 10327 18500343 125 128 ADH Gene 10327 18500343 164 167 ADH Gene 10327 18500343 213 219 cancer Disease D009369 18500343 301 306 ADH1B Gene 125 18500343 323 327 ADH7 Gene 131 18500343 381 387 cancer Disease D009369 18500343 505 535 increasing alcohol consumption Environment 125-D009369 18500343 505 535 increasing alcohol consumption Environment 131-D009369 18500343 657 660 ADH Gene 10327 18500343 706 712 cancer Disease D009369 17404387|t|Pooled analysis and meta-analysis of the glutathione S-transferase P1 Ile 105Val polymorphism and bladder cancer: a HuGE-GSEC review. 17404387|t|The glutathione S-transferase P1 genotype (GSTP1) is involved in the inactivation of cigarette smoke carcinogens, and sequence variation in the gene may alter bladder cancer susceptibility. To examine the association between GSTP1Ile 105Val and bladder cancer, the authors undertook a meta- and pooled analysis. Summary crude and adjusted odds ratios and corresponding 95% confidence intervals were pooled by using a random-effects model. In the meta-analysis (16 studies, 4,273 cases and 5,081 controls), the unadjusted summary odds ratios for GSTP1 Ile/Val and Val/Val compared with GSTP1 Ile/Ile were 1.54 (95% confidence interval: 1.21, 1.99; p < 0.001) and 2.17 (95% confidence interval: 1.27, 3.71; p = 0.005). The association appeared to be the strongest in Asian countries. When the analysis was limited to European descendents (nine studies), the summary odds ratio decreased (odds ratio = 1.24, 95% confidence interval: 1.00, 1.52) (Q = 17.50; p = 0.02). All relevant data previously contributed to the International Study on Genetic Susceptibility to Environmental Carcinogens were pooled (eight studies, 1,305 cases and 1,558 controls). The summary odds ratios were similar to the ones from the meta-analysis. Case-only analyses did not detect an interaction between the GSTP1 genotype and smoking status (never/ever). GSTP1 Ile 105Val appears to be associated with a modest increase in the risk of bladder cancer. 17404387 41 69 glutathione S-transferase P1 Gene 2950 17404387 98 112 bladder cancer Disease D001749 17404387 4 32 glutathione S-transferase P1 Gene 2950 17404387 43 48 GSTP1 Gene 2950 17404387 159 173 bladder cancer Disease D001749 17404387 225 230 GSTP1 Gene 2950 17404387 245 259 bladder cancer Disease D001749 17404387 545 550 GSTP1 Gene 2950 17404387 585 590 GSTP1 Gene 2950 17404387 765 780 Asian countries Environment 2950-D001749 17404387 1036 1058 Genetic Susceptibility Disease D020022 17404387 1283 1288 GSTP1 Gene 2950 17404387 1331 1336 GSTP1 Gene 2950 17404387 1411 1425 bladder cancer Disease D001749 11815396|t|Genetic polymorphisms in N-acetyltransferase-2 and microsomal epoxide hydrolase, cumulative cigarette smoking, and lung cancer. 11815396|t|N-acetyltrasferase-2 (NAT2) and microsomal epoxide hydrolase (mEH) are polymorphic genes that metabolize different tobacco carcinogens. Smaller studies found inconsistent relationships between NAT2 or mEH polymorphisms and lung cancer risk. To determine whether there is gene-environment interaction between NAT2 polymorphisms, alone or in combination with mEH polymorphisms, and cumulative smoking exposure in the development of lung cancer, we conducted a case control study of 1115 Caucasian lung cancer patients and 1250 spouse and friend controls. The results were analyzed using generalized additive models and logistic regression, adjusting for relevant covariates. There was no overall relationship between NAT2 genotype and lung cancer risk; the adjusted odds ratio (OR) of the rapid versus slow acetylator genotypes was 0.96 [95% confidence interval (CI), 0.79-1.16]. However, gene-environment interaction analyses revealed that the adjusted ORs increased significantly as pack-years increased. For nonsmokers, the fitted OR was 0.66 (95% CI, 0.44-0.99), whereas for heavy smokers (80 pack-years), the OR increased to 1.22 (95% CI, 0.89-1.67). When comparing the extreme genotype combinations of the NAT2 rapid acetylator, higher mEH activity genotype to the NAT2 slow acetylator, and very low mEH activity genotype, the corresponding ORs at 0 and 80 pack-years were 0.30 (95% CI, 0.14-0.62) and 2.19 (95% CI, 1.26-3.81), respectively. Results were similar with ORs derived from stratified models. In conclusion, NAT2 rapid acetylator genotypes are protective against lung cancer in nonsmokers but are risk factors in heavy smokers. The joint effects of NAT2 and mEH polymorphisms are consistent with an independent, additive effect of these two genes, modified by smoking history. 11815396 25 46 N-acetyltransferase-2 Gene 10 11815396 51 79 microsomal epoxide hydrolase Gene 2052 11815396 115 126 lung cancer Disease D008175 11815396 0 20 N-acetyltrasferase-2 Gene 10 11815396 22 26 NAT2 Gene 10 11815396 32 60 microsomal epoxide hydrolase Gene 2052 11815396 62 65 mEH Gene 2052 11815396 193 197 NAT2 Gene 10 11815396 201 204 mEH Gene 2052 11815396 223 234 lung cancer Disease D008175 11815396 308 312 NAT2 Gene 10 11815396 357 360 mEH Gene 2052 11815396 430 441 lung cancer Disease D008175 11815396 495 506 lung cancer Disease D008175 11815396 715 719 NAT2 Gene 10 11815396 733 744 lung cancer Disease D008175 11815396 983 1003 pack-years increased Environment 10-D008175 11815396 1009 1019 nonsmokers Environment 10-D008175 11815396 1077 1106 heavy smokers (80 pack-years) Environment 10-D008175 11815396 1210 1214 NAT2 Gene 10 11815396 1240 1243 mEH Gene 2052 11815396 1269 1273 NAT2 Gene 10 11815396 1304 1307 mEH Gene 2052 11815396 1352 1371 0 and 80 pack-years Environment 2052-D008175 11815396 1352 1371 0 and 80 pack-years Environment 10-D008175 11815396 1523 1527 NAT2 Gene 10 11815396 1578 1589 lung cancer Disease D008175 11815396 1593 1603 nonsmokers Environment 10-D008175 11815396 1628 1641 heavy smokers Environment 10-D008175 11815396 1664 1668 NAT2 Gene 10 11815396 1673 1676 mEH Gene 2052 11815396 1775 1790 smoking history Environment 2052-D008175 11815396 1775 1790 smoking history Environment 10-D008175 9699660|t|A prospective study of N-acetyltransferase genotype, red meat intake, and risk of colorectal cancer. 9699660|t|Carcinogenic heterocyclic amines are activated by N-acetyltransferase (NAT) enzymes, encoded by NAT1 and NAT2, to genotoxic compounds that can form DNA adducts in the colon epithelium. We have examined the relation of polymorphisms in the genes coding for both enzymes to risk of colorectal cancer and the gene-environment interaction with red meat intake among participants in the prospective Physicians' Health Study. Baseline blood samples from 212 men subsequently diagnosed with colorectal cancer during 13 years of follow-up were genotyped, along with 221 controls. NAT genotypes were analyzed by a PCR-restriction fragment length polymorphism method. Effect modification of the relation of red meat intake and risk of colorectal cancer by NAT genotype was assessed using conditional logistic regression. There was no overall independent association of NAT acetylation genotypes and colorectal cancer risk. The relative risks for the rapid acetylation genotype were 0.93 [95% confidence interval (CI), 0.61-1.42] for NAT1, 0.80 (95% CI, 0.53-1.19) for NAT2, and 0.81 (95% CI, 0.52-1.27) for NAT1/NAT2 combined. We observed a stronger association of red meat intake with cancer risk among NAT rapid acetylators, especially among men 60 years old or older. Among those men who were rapid acetylators for both NAT1 and NAT2, consumption of >1 serving of red meat per day was associated with a relative risk of 5.82 (95% CI, 1.11-30.6) compared with consumption of < or = 0.5 serving per day (P, trend = 0.02). These prospective data, which need to be confirmed in other studies, suggest that polymorphisms in the NAT genes confer differential susceptibility to the effect of red meat consumption on colorectal cancer risk. 9699660 23 42 N-acetyltransferase Gene 6046 9699660 82 99 colorectal cancer Disease D015179 9699660 0 12 Carcinogenic Disease D063646 9699660 50 69 N-acetyltransferase Gene 6046 9699660 71 74 NAT Gene 6046 9699660 96 100 NAT1 Gene 9 9699660 105 109 NAT2 Gene 10 9699660 280 297 colorectal cancer Disease D015179 9699660 484 501 colorectal cancer Disease D015179 9699660 572 575 NAT Gene 6046 9699660 725 742 colorectal cancer Disease D015179 9699660 746 749 NAT Gene 6046 9699660 859 862 NAT Gene 6046 9699660 889 906 colorectal cancer Disease D015179 9699660 1023 1027 NAT1 Gene 9 9699660 1058 1062 NAT2 Gene 10 9699660 1097 1101 NAT1 Gene 9 9699660 1102 1106 NAT2 Gene 10 9699660 1155 1170 red meat intake Environment 10-D015179 9699660 1155 1170 red meat intake Environment 9-D015179 9699660 1176 1182 cancer Disease D009369 9699660 1194 1197 NAT Gene 6046 9699660 1313 1317 NAT1 Gene 9 9699660 1322 1326 NAT2 Gene 10 9699660 1616 1619 NAT Gene 6046 9699660 1678 1698 red meat consumption Environment 10-D015179 9699660 1678 1698 red meat consumption Environment 9-D015179 9699660 1702 1719 colorectal cancer Disease D015179 19125104|t|Trajectories of depressive symptoms, dopamine D2 and D4 receptors, family socioeconomic status and social support in adolescence and young adulthood. 19125104|t|OBJECTIVES: The purpose of this study is two-fold. First, we tested the association between dopamine D2 and D4 receptors and a trajectory of depressive symptoms in adolescence and young adulthood. Second, we reestimated the association between the dopamine receptors and depression after taking into account the effects of socioeconomic disparity and child-parent ties and social support. METHODS: The study uses the DNA sample of approximately 2500 individuals in the National Longitudinal Study of Adolescent Health (Add Health). Each individual was measured three times in 1994, 1996, and 2002. RESULTS: This study has yielded robust associations of the DRD2 and DRD4 variants with depressive symptoms among male adolescents and young adults. The DRD2*304/178 genotype is associated with a level of depressive symptoms 0.04-0.07 points (3-5% of the mean) higher than the DRD2*178/178 genotype. Relative to the other more common DRD4 variants, the DRD4*379/379 genotype raises the level of depression by about 0.25 points (about 17% of the mean). These findings hold after adjusting for the effects of socioeconomic status (family structure, parental education, family income, mother's employment status, and whether attending public school) and child-parent ties/social support (conflict with parent(s), closeness to parent(s), parental availability, and social support). Although the gene-sex interaction is clearly present, the tests of gene-lifecourse interaction did not yield any significant results. CONCLUSION: Our findings emphasize the importance of joint influences of genetic propensities and social environment on depressive symptoms. 19125104 16 35 depressive symptoms Disease D003866 19125104 141 160 depressive symptoms Disease D003866 19125104 271 281 depression Disease D003866 19125104 657 661 DRD2 Gene 1813 19125104 666 670 DRD4 Gene 1815 19125104 685 704 depressive symptoms Disease D003866 19125104 750 754 DRD2 Gene 1813 19125104 802 821 depressive symptoms Disease D003866 19125104 874 878 DRD2 Gene 1813 19125104 931 935 DRD4 Gene 1815 19125104 950 954 DRD4 Gene 1815 19125104 992 1002 depression Disease D003866 19125104 1393 1396 sex Environment 1815-D003866 19125104 1393 1396 sex Environment 1813-D003866 19125104 1629 1648 depressive symptoms Disease D003866 21150883|t|Prevalence of CDKN2A mutations in pancreatic cancer patients: implications for genetic counseling. 21150883|t|Germline mutations in CDKN2A have been reported in pancreatic cancer families, but genetic counseling for pancreatic cancer risk has been limited by lack of information on CDKN2A mutation carriers outside of selected pancreatic or melanoma kindreds. Lymphocyte DNA from consecutive, unselected white non-Hispanic patients with pancreatic adenocarcinoma was used to sequence CDKN2A. Frequencies of mutations that alter the coding of p16INK4 or p14ARF were quantified overall and in subgroups. Penetrance and likelihood of carrying mutations by family history were estimated. Among 1537 cases, 9 (0.6%) carried germline mutations in CDKN2A, including three previously unreported mutations. CDKN2A mutation carriers were more likely to have a family history of pancreatic cancer (P=0.003) or melanoma (P=0.03), and a personal history of melanoma (P=0.01). Among cases who reported having a first-degree relative with pancreatic cancer or melanoma, the carrier proportions were 3.3 and 5.3%, respectively. Penetrance for mutation carriers by age 80 was calculated to be 58% for pancreatic cancer (95% confidence interval (CI) 8-86%), and 39% for melanoma (95% CI 0-80). Among cases who ever smoked cigarettes, the risk for pancreatic cancer was higher for carriers compared with non-carriers (HR 25.8, P=2.1 x 10(-)(1)(3)), but among nonsmokers, this comparison did not reach statistical significance. Germline mutations in CDKN2A among unselected pancreatic cancer patients are uncommon, although notably penetrant, especially among smokers. Carriers of germline mutations of CDKN2A should be counseled to avoid tobacco use to decrease risk of pancreatic cancer in addition to taking measures to decrease melanoma risk. 21150883 14 20 CDKN2A Gene 1029 21150883 34 51 pancreatic cancer Disease D010190 21150883 22 28 CDKN2A Gene 1029 21150883 51 68 pancreatic cancer Disease D010190 21150883 106 123 pancreatic cancer Disease D010190 21150883 172 178 CDKN2A Gene 1029 21150883 231 239 melanoma Disease D008545 21150883 338 352 adenocarcinoma Disease D000230 21150883 374 380 CDKN2A Gene 1029 21150883 432 439 p16INK4 Gene 1029 21150883 443 449 p14ARF Gene 1029 21150883 631 637 CDKN2A Gene 1029 21150883 688 694 CDKN2A Gene 1029 21150883 758 775 pancreatic cancer Disease D010190 21150883 789 797 melanoma Disease D008545 21150883 834 842 melanoma Disease D008545 21150883 914 931 pancreatic cancer Disease D010190 21150883 935 943 melanoma Disease D008545 21150883 1038 1044 age 80 Environment 1029-D010190 21150883 1038 1044 age 80 Environment 1029-D008545 21150883 1074 1091 pancreatic cancer Disease D010190 21150883 1142 1150 melanoma Disease D008545 21150883 1178 1204 who ever smoked cigarettes Environment 1029-D010190 21150883 1219 1236 pancreatic cancer Disease D010190 21150883 1420 1426 CDKN2A Gene 1029 21150883 1444 1461 pancreatic cancer Disease D010190 21150883 1530 1537 smokers Environment 1029-D010190 21150883 1573 1579 CDKN2A Gene 1029 21150883 1609 1620 tobacco use Environment 1029-D010190 21150883 1641 1658 pancreatic cancer Disease D010190 21150883 1702 1710 melanoma Disease D008545 19996973|t|N-acetyltransferase 2, exposure to aromatic and heterocyclic amines, and receptor-defined breast cancer. 19996973|t|The role of N-acetyltransferase 2 (NAT2) polymorphism in breast cancer is still unclear. We explored the associations between potential sources of exposure to aromatic and heterocyclic amines (AHA), acetylation status and receptor-defined breast cancer in 1020 incident cases and 1047 population controls of the German GENICA study. Acetylation status was assessed as slow or fast. Therefore, NAT2 haplotypes were estimated using genotype information from six NAT2 polymorphisms. Most probable haplotypes served as alleles for the deduction of NAT2 acetylation status. The risks of developing estrogen receptor alpha (ER) and progesterone receptor (PR)-positive or negative tumors were estimated for tobacco smoking, consumption of red meat, grilled food, coffee, and tea, as well as expert-rated occupational exposure to AHA with logistic regression conditional on age and adjusted for potential confounders. Joint effects of these factors and NAT2 acetylation status were investigated. Frequent consumption of grilled food and coffee showed higher risks in slow acetylators for receptor-negative tumors [grilled food: ER-: odds ratio (OR) 2.57, 95% confidence interval (CI) 1.07-6.14 for regular vs. rare; coffee: ER-: OR 2.55, 95% CI 1.22-5.33 for >or=4 vs. 0 cups/day]. We observed slightly higher risks for never smokers that are fast acetylators for receptor-positive tumors compared with slow acetylators (ER-: OR 1.32, 95% CI 1.00-1.73). Our results support differing risk patterns for receptor-defined breast cancer. However, the modifying role of NAT2 for receptor-defined breast cancer is difficult to interpret in the light of complex mixtures of exposure to AHA. 19996973 0 21 N-acetyltransferase 2 Gene 10 19996973 90 103 breast cancer Disease D001943 19996973 12 33 N-acetyltransferase 2 Gene 10 19996973 35 39 NAT2 Gene 10 19996973 57 70 breast cancer Disease D001943 19996973 239 252 breast cancer Disease D001943 19996973 393 397 NAT2 Gene 10 19996973 460 464 NAT2 Gene 10 19996973 544 548 NAT2 Gene 10 19996973 593 616 estrogen receptor alpha Gene 2099 19996973 626 647 progesterone receptor Gene 5241 19996973 649 651 PR Gene 5241 19996973 674 680 tumors Disease D009369 19996973 945 949 NAT2 Gene 10 19996973 988 1035 Frequent consumption of grilled food and coffee Environment 10-D001943 19996973 1098 1104 tumors Disease D009369 19996973 1312 1325 never smokers Environment 10-D001943 19996973 1374 1380 tumors Disease D009369 19996973 1511 1524 breast cancer Disease D001943 19996973 1557 1561 NAT2 Gene 10 19996973 1583 1596 breast cancer Disease D001943 20658464|t|Polymorphism in xeroderma pigmentosum complementation group C codon 939 and aflatoxin B1-related hepatocellular carcinoma in the Guangxi population. 20658464|t|UNLABELLED: Genetic polymorphisms in DNA repair genes may influence individual variations in DNA repair capacity, and this may be associated with the risk and outcome of hepatocellular carcinoma (HCC) related to aflatoxin B1 (AFB1) exposure. In this study, we focused on the polymorphism of xeroderma pigmentosum complementation group C (XPC) codon 939 (rs#2228001), which is involved in nucleotide excision repair. We conducted a case-control study including 1156 HCC cases and 1402 controls without any evidence of hepatic disease to evaluate the associations between this polymorphism and HCC risk and prognosis in the Guangxi population. AFB1 DNA adduct levels, XPC genotypes, and XPC protein levels were tested with a comparative enzyme-linked immunosorbent assay, TaqMan polymerase chain reaction for XPC genotypes, and immunohistochemistry, respectively. Higher AFB1 exposure was observed among HCC patients versus the control group [odds ratio (OR) = 9.88 for AFB1 exposure years and OR = 6.58 for AFB1 exposure levels]. The XPC codon 939 Gln alleles significantly increased HCC risk [OR = 1.25 (95% confidence interval = 1.03-1.52) for heterozygotes of the XPC codon 939 Lys and Gln alleles (XPC-LG) and OR = 1.81 (95% confidence interval = 1.36-2.40) for homozygotes of the XPC codon 939 Gln alleles (XPC-GG)]. Significant interactive effects between genotypes and AFB1 exposure status were also observed in the joint-effects analysis. This polymorphism, moreover, was correlated with XPC expression levels in cancerous tissues (r = -0.369, P < 0.001) and with the overall survival of HCC patients (the median survival times were 30, 25, and 19 months for patients with homozygotes of the XPC codon 939 Lys alleles, XPC-LG, and XPC-GG, respectively), especially under high AFB1 exposure conditions. Like AFB1 exposure, the XPC codon 939 polymorphism was an independent prognostic factor influencing the survival of HCC. Additionally, this polymorphism multiplicatively interacted with the xeroderma pigmentosum complementation group D codon 751 polymorphism with respect to HCC risk (OR(interaction) = 1.71). CONCLUSION: These results suggest that the XPC codon 939 polymorphism may be associated with the risk and outcome of AFB1-related HCC in the Guangxi population and may interact with AFB1 exposure in the process of HCC induction by AFB1. 20658464 16 61 xeroderma pigmentosum complementation group C Gene 7508 20658464 16 25 xeroderma Disease D007057 20658464 97 121 hepatocellular carcinoma Disease D006528 20658464 170 194 hepatocellular carcinoma Disease D006528 20658464 196 199 HCC Disease D006528 20658464 291 336 xeroderma pigmentosum complementation group C Gene 7508 20658464 291 300 xeroderma Disease D007057 20658464 338 341 XPC Gene 7508 20658464 465 468 HCC Disease D006528 20658464 517 532 hepatic disease Disease 1 20658464 592 595 HCC Disease D006528 20658464 666 669 XPC Gene 7508 20658464 685 688 XPC Gene 7508 20658464 807 810 XPC Gene 7508 20658464 902 905 HCC Disease D006528 20658464 1033 1036 XPC Gene 7508 20658464 1083 1086 HCC Disease D006528 20658464 1166 1169 XPC Gene 7508 20658464 1201 1204 XPC Gene 7508 20658464 1284 1287 XPC Gene 7508 20658464 1311 1314 XPC Gene 7508 20658464 1375 1395 AFB1 exposure status Environment 7508-D006528 20658464 1495 1498 XPC Gene 7508 20658464 1595 1598 HCC Disease D006528 20658464 1699 1702 XPC Gene 7508 20658464 1726 1729 XPC Gene 7508 20658464 1738 1741 XPC Gene 7508 20658464 1778 1807 high AFB1 exposure conditions Environment 7508-D006528 20658464 1833 1836 XPC Gene 7508 20658464 1925 1928 HCC Disease D006528 20658464 1999 2008 xeroderma Disease D007057 20658464 2084 2087 HCC Disease D006528 20658464 2162 2165 XPC Gene 7508 20658464 2236 2240 AFB1 Environment 7508-D006528 20658464 2249 2252 HCC Disease D006528 20658464 2301 2314 AFB1 exposure Environment 7508-D006528 20658464 2333 2336 HCC Disease D006528 20658464 2350 2354 AFB1 Environment 7508-D006528 15563601|t|Social supports and serotonin transporter gene moderate depression in maltreated children. 15563601|t|In this study, measures of the quality and availability of social supports were found to moderate risk for depression associated with a history of maltreatment and the presence of the short (s) allele of the serotonin transporter gene promoter polymorphism (5-HTTLPR). The present investigation (i) replicates research in adults showing that 5-HTTLPR variation moderates the development of depression after stress, (ii) extends the finding to children, and (iii) demonstrates the ability of social supports to further moderate risk for depression. Maltreated children with the s/s genotype and no positive supports had the highest depression ratings, scores that were twice as high as the non-maltreated comparison children with the same genotype. However, the presence of positive supports reduced risk associated with maltreatment and the s/s genotype, such that maltreated children with this profile had only minimal increases in their depression scores. These findings are consistent with emerging preclinical and clinical data suggesting that the negative sequelae associated with early stress are not inevitable. Risk for negative outcomes may be modified by both genetic and environmental factors, with the quality and availability of social supports among the most important environmental factors in promoting resiliency in maltreated children, even in the presence of a genotype expected to confer vulnerability for psychiatric disorder. 15563601 0 15 Social supports Environment 6532-D003866 15563601 20 41 serotonin transporter Gene 6532 15563601 56 66 depression Disease D003866 15563601 107 117 depression Disease D003866 15563601 208 229 serotonin transporter Gene 6532 15563601 390 400 depression Disease D003866 15563601 536 546 depression Disease D003866 15563601 631 641 depression Disease D003866 15563601 757 790 the presence of positive supports Environment 6532-D003866 15563601 939 949 depression Disease D003866 15563601 1210 1257 the quality and availability of social supports Environment 6532-D003866 15563601 1425 1445 psychiatric disorder Disease D001523 7616113|t|Association between serum lipids and apolipoprotein E phenotype is influenced by diet in a population-based sample of free-living children and young adults: the Cardiovascular Risk in Young Finns Study. 7616113|t|Apolipoprotein E (apoE) is a genetic determinant of coronary heart disease and lipid levels in several populations. We studied whether the association of apoE alleles with serum lipids varies with diet in a population of free-living young Finns. One thousand twelve subjects, aged 9-24 years, were studied as a part of the Cardiovascular Risk in Young Finns Study in 1986. Serum lipid concentrations and apoE phenotypes were determined, and the composition of the diet was assessed by the 48-h recall method. The subjects were divided into three groups according to the intake of dietary saturated fatty acids (SAFA, g/1000 kcal) and cholesterol (mg/1000 kcal). Group one (high SAFA-cholesterol group) was formed from subjects belonging to the highest tertiles of both cholesterol and SAFA intakes (n = 175); group two (middle SAFA-cholesterol group) consisted of subjects belonging to the middle respective tertiles (n = 119); and group three (low SAFA-cholesterol group) consisted of subjects belonging to the lowest respective tertiles (n = 192). The statistical significance of the association of serum total cholesterol and low density lipoprotein (LDL) concentration with apoE phenotype increased from the low SAFA-cholesterol group (P = 0.024 for total cholesterol and P = 0.015 for LDL-cholesterol, respectively) to the high SAFA-cholesterol group (P = 0.0022 and P = 0.00073, respectively). The middle SAFA-cholesterol group fell between these two groups.(ABSTRACT TRUNCATED AT 250 WORDS) 7616113 37 53 apolipoprotein E Gene 348 7616113 0 16 Apolipoprotein E Gene 348 7616113 18 22 apoE Gene 348 7616113 52 74 coronary heart disease Disease D003327 7616113 154 158 apoE Gene 348 7616113 404 408 apoE Gene 348 7616113 1178 1182 apoE Gene 348 7616113 1208 1238 the low SAFA-cholesterol group Environment 348-D003327 7616113 1324 1355 the high SAFA-cholesterol group Environment 348-D003327 19706757|t|Polymorphisms in DNA repair genes, smoking, and bladder cancer risk: findings from the international consortium of bladder cancer. 19706757|t|Tobacco smoking is the most important and well-established bladder cancer risk factor and a rich source of chemical carcinogens and reactive oxygen species that can induce damage to DNA in urothelial cells. Therefore, common variation in DNA repair genes might modify bladder cancer risk. In this study, we present results from meta-analyses and pooled analyses conducted as part of the International Consortium of Bladder Cancer. We included data on 10 single nucleotide polymorphisms corresponding to seven DNA repair genes from 13 studies. Pooled analyses and meta-analyses included 5,282 cases and 5,954 controls of non-Latino white origin. We found evidence for weak but consistent associations with ERCC2 D312N [rs1799793; per-allele odds ratio (OR), 1.10; 95% confidence interval (95% CI), 1.01-1.19; P = 0.021], NBN E185Q (rs1805794; per-allele OR, 1.09; 95% CI, 1.01-1.18; P = 0.028), and XPC A499V (rs2228000; per-allele OR, 1.10; 95% CI, 1.00-1.21; P = 0.044). The association with NBN E185Q was limited to ever smokers (interaction P = 0.002) and was strongest for the highest levels of smoking dose and smoking duration. Overall, our study provides the strongest evidence to date for a role of common variants in DNA repair genes in bladder carcinogenesis. 19706757 48 62 bladder cancer Disease D001749 19706757 115 129 bladder cancer Disease D001749 19706757 59 73 bladder cancer Disease D001749 19706757 268 282 bladder cancer Disease D001749 19706757 415 429 Bladder Cancer Disease D001749 19706757 705 710 ERCC2 Gene 2068 19706757 1018 1030 ever smokers Environment 2683-D001749 19706757 1077 1132 the highest levels of smoking dose and smoking duration Environment 2683-D001749 19706757 1254 1268 carcinogenesis Disease D063646 17181859|t|Genetic polymorphisms in the cyclooxygenase-2 gene, use of nonsteroidal anti-inflammatory drugs, and breast cancer risk. 17181859|t|INTRODUCTION: The association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer risk remains unclear. Inconsistencies in previously reported findings may be partly due to differences in expression of cyclooxygenase (COX)-2. We hypothesized that genetic polymorphisms (COX-2 .926, COX-2 .5209, and COX-2 .8473) may reduce overall breast cancer risk or risk for subtypes of breast cancer by modulating the inflammatory response and may interact with aspirin or any NSAID use. METHODS: We conducted a population-based, case-control study in which we genotyped 1,067 breast cancer cases and 1,110 control individuals included in the Long Island Breast Cancer Study Project. RESULTS: No major effects of the three COX-2 variant alleles on breast cancer risk were found. A total of eight distinct haplotypes and 18 diplotypes were observed in the population. Overall, no significant associations between COX-2 haplotypes/diplotypes and breast cancer risk were observed. Among women who used aspirin or any NSAID there was little evidence for an interaction with the at-risk COX-2 genotypes, with one exception. Among women with hormone receptor positive breast cancer, the reduced risk for any NSAID use was only evident among those who had at least one variant C allele of COX-2 .8473 (odds ratio = 0.7, 95% confidence interval = 0.5 to 1.0; P for the interaction = 0.02). There was no corresponding interaction for aspirin use, possibly because of limited power. CONCLUSION: These data provide modest evidence that the C allele of COX-2 .8473 may interact with NSAIDs to reduce risk for hormone receptor positive breast cancer. 17181859 29 45 cyclooxygenase-2 Gene 5743 17181859 101 114 breast cancer Disease D001943 17181859 95 108 breast cancer Disease D001943 17181859 229 251 cyclooxygenase (COX)-2 Gene 4513 17181859 297 302 COX-2 Gene 4513 17181859 309 314 COX-2 Gene 4513 17181859 326 331 COX-2 Gene 4513 17181859 358 371 breast cancer Disease D001943 17181859 401 414 breast cancer Disease D001943 17181859 592 605 breast cancer Disease D001943 17181859 738 743 COX-2 Gene 4513 17181859 763 776 breast cancer Disease D001943 17181859 927 932 COX-2 Gene 4513 17181859 959 972 breast cancer Disease D001943 17181859 1097 1102 COX-2 Gene 4513 17181859 1151 1167 hormone receptor Gene 3164 17181859 1177 1190 breast cancer Disease D001943 17181859 1213 1226 any NSAID use Environment 4513-D001943 17181859 1297 1302 COX-2 Gene 4513 17181859 1556 1561 COX-2 Gene 4513 17181859 1586 1592 NSAIDs Environment 4513-D001943 17181859 1612 1628 hormone receptor Gene 3164 17181859 1638 1651 breast cancer Disease D001943 19899843|t|Children's inferential styles, 5-HTTLPR genotype, and maternal expressed emotion-criticism: An integrated model for the intergenerational transmission of depression. 19899843|t|The authors tested a model for the intergenerational transmission of depression integrating specific genetic (5-HTTLPR), cognitive (inferential style), and environmental (mother depressive symptoms and expressed-emotion criticism [EE-Crit]) risk factors. Supporting the hypothesis that maternal depression is associated with elevated levels of stress in children's lives, mothers with a history of major depressive disorder (MDD) exhibited higher depressive symptoms across a 6-month multiwave follow-up than mothers with no depression history. In addition, partially supporting our hypothesis, levels of maternal criticism during the follow-up were significantly related to mothers' current depressive symptoms but not to history of MDD. Finally, the authors found support for an integrated Gene x Cognition x Environment model of risk. Specifically, among children with negative inferential styles regarding their self-characteristics, there was a clear dose response of 5-HTTLPR genotype moderating the relation between maternal criticism and children's depressive symptoms, with the highest depressive symptoms during the follow-up observed among children carrying 2 copies of the 5-HTTLPR lower expressing alleles (short [S] or long [LG]) who also exhibited negative inferential styles for self-characteristics and who experienced high levels of EE-Crit. In contrast, children with positive inferential styles exhibited low depressive symptoms regardless of 5-HTTLPR genotype or level of maternal criticism. 19899843 31 39 5-HTTLPR Gene 6532 19899843 154 164 depression Disease D003866 19899843 69 79 depression Disease D003866 19899843 110 118 5-HTTLPR Gene 6532 19899843 178 197 depressive symptoms Disease D003866 19899843 295 305 depression Disease D003866 19899843 398 423 major depressive disorder Disease D003865 19899843 425 428 MDD Disease D003865 19899843 447 466 depressive symptoms Disease D003866 19899843 525 535 depression Disease D003866 19899843 692 711 depressive symptoms Disease D003866 19899843 734 737 MDD Disease D003865 19899843 858 899 children with negative inferential styles Environment 6532-D003866 19899843 973 981 5-HTTLPR Gene 6532 19899843 1057 1076 depressive symptoms Disease D003866 19899843 1095 1114 depressive symptoms Disease D003866 19899843 1185 1193 5-HTTLPR Gene 6532 19899843 1263 1315 negative inferential styles for self-characteristics Environment 6532-D003866 19899843 1336 1358 high levels of EE-Crit Environment 6532-D003866 19899843 1429 1448 depressive symptoms Disease D003866 19899843 1463 1471 5-HTTLPR Gene 6532 19618370|t|Functional FEN1 polymorphisms are associated with DNA damage levels and lung cancer risk. 19618370|t|Flap endonuclease 1 (FEN1) is a key enzyme in maintaining genomic stability and protecting against carcinogenesis. This study investigated whether functional variations in FEN1 gene are associated with DNA damage and lung cancer risk. Thirty DNA samples were sequenced to identify variants and function of the variants was examined by a set of biochemical assays. DNA damage levels were detected by comet assays in a cohort of 303 coke-oven workers and 297 controls. The association with lung cancer risk was examined in two independent case-control panels consisted of a total 1,840 lung cancer patients and 1,958 controls. We identified two single nucleotide polymorphisms (SNPs) located in the FEN1 promoter c.-69G>A (rs174538:G>A) and 3'-untranslational region c.4150G>T (rs4246215:G>T) that were associated with reduced FEN1 expression. Among coke-oven workers, DNA damage levels were significantly higher in the -69GG or GA carriers compared with the -69AA carriers. The -69GG or 4150GG carriers had a significantly increased risk for developing lung cancer compared with the -69AA or 4150TT carriers. These results highlight FEN1 as an important gene in human carcinogenesis and genetic polymorphisms in FEN1 confer susceptibility to lung cancer. 19618370 11 15 FEN1 Gene 2237 19618370 72 83 lung cancer Disease D008175 19618370 0 19 Flap endonuclease 1 Gene 2237 19618370 21 25 FEN1 Gene 2237 19618370 58 75 genomic stability Disease D042822 19618370 99 113 carcinogenesis Disease D063646 19618370 172 176 FEN1 Gene 2237 19618370 217 228 lung cancer Disease D008175 19618370 488 499 lung cancer Disease D008175 19618370 584 595 lung cancer Disease D008175 19618370 697 701 FEN1 Gene 2237 19618370 825 829 FEN1 Gene 2237 19618370 848 865 coke-oven workers Environment 2237-D008175 19618370 1052 1063 lung cancer Disease D008175 19618370 1132 1136 FEN1 Gene 2237 19618370 1167 1181 carcinogenesis Disease D063646 19618370 1211 1215 FEN1 Gene 2237 19618370 1241 1252 lung cancer Disease D008175 17974934|t|The serotonin transporter genotype and social support and moderation of posttraumatic stress disorder and depression in hurricane-exposed adults. 17974934|t|OBJECTIVE: Disasters are associated with increased risk of posttraumatic stress disorder (PTSD) and major depression, but no study, to the authors' knowledge, has determined whether genotype interacts with disaster exposure and social support to moderate risk of these phenotypes. The authors tested the hypothesis that a polymorphism in the serotonin transporter gene (locus, SLC6A4; variant, serotonin 5-HTTLPR) moderates risk of posthurricane PTSD and major depression given high hurricane exposure and low social support. METHOD: The authors interviewed a household probability sample of adults 6-9 months after the 2004 hurricanes about hurricane exposure, social support, and posthurricane PTSD and major depression. DNA was collected from a subset of participants. Participants were 589 adults ages 18 and older from 38 Florida counties who provided valid DNA samples. Outcome measures were DSM-IV diagnoses of posthurricane PTSD and major depression derived from structured interviews. RESULTS: The low-expression variant of the 5-HTTLPR polymorphism increased risk of posthurricane PTSD and major depression but only under the conditions of high hurricane exposure and low social support after adjustment for sex, ancestry (as determined by Bayesian clustering of genotypes), and age. Similar effects were found for major depression. High-risk individuals (high hurricane exposure, the low-expression 5-HTTLPR variant, low social support) were at 4.5 times the risk of developing PTSD and major depression of low-risk individuals. CONCLUSIONS: The low-expression variant of the 5-HTTLPR polymorphism modifies risk of postdisaster PTSD and major depression under conditions of high hurricane exposure and low social support, confirming and extending previous research. 17974934 4 25 serotonin transporter Gene 6532 17974934 72 101 posttraumatic stress disorder Disease D013313 17974934 106 116 depression Disease D003866 17974934 59 88 posttraumatic stress disorder Disease D013313 17974934 90 94 PTSD Disease D013313 17974934 100 116 major depression Disease D003865 17974934 342 363 serotonin transporter Gene 6532 17974934 377 383 SLC6A4 Gene 6532 17974934 446 450 PTSD Disease D013313 17974934 455 471 major depression Disease D003865 17974934 696 700 PTSD Disease D013313 17974934 705 721 major depression Disease D003865 17974934 932 936 PTSD Disease D013313 17974934 941 957 major depression Disease D003865 17974934 1091 1095 PTSD Disease D013313 17974934 1100 1116 major depression Disease D003865 17974934 1150 1173 high hurricane exposure Environment 6532-D003865 17974934 1150 1173 high hurricane exposure Environment 6532-D013313 17974934 1178 1196 low social support Environment 6532-D003865 17974934 1178 1196 low social support Environment 6532-D013313 17974934 1325 1341 major depression Disease D003865 17974934 1366 1389 high hurricane exposure Environment 6532-D003865 17974934 1366 1389 high hurricane exposure Environment 6532-D013313 17974934 1428 1446 low social support Environment 6532-D003865 17974934 1428 1446 low social support Environment 6532-D013313 17974934 1489 1493 PTSD Disease D013313 17974934 1498 1514 major depression Disease D003865 17974934 1639 1643 PTSD Disease D013313 17974934 1648 1664 major depression Disease D003865 17974934 1685 1708 high hurricane exposure Environment 6532-D003865 17974934 1685 1708 high hurricane exposure Environment 6532-D013313 17974934 1713 1731 low social support Environment 6532-D003865 17974934 1713 1731 low social support Environment 6532-D013313 18757527|t|Apoptosis gene polymorphisms, age, smoking and the risk of non-small cell lung cancer. 18757527|t|Apoptosis is important for targeting cancer cells for destruction. Various single-nucleotide polymorphisms (SNPs) in apoptotic genes have been associated with increased risks in lung cancer, particularly FAS -1377 G>A (rs2234767), FASLG -844 C>T (rs763110), IL1B +3954 C>T Phe105Phe (rs1143634) and BAT3 Ser625Pro (rs1052486). We studied the association of these SNPs with non-small cell lung cancer (NSCLC) in a large case-control study (N = 4263: 2644 cases and 1619 controls). No associations with NSCLC were observed in the main effects analysis for all four SNPs, adjusting for age, gender, smoking status, pack-years and years since smoking cessation. In subjects under age 60, for FASLG -844 C>T polymorphism, CT compared with the CC genotype, was significantly associated with increased risk of NSCLC, adjusted odds ratio (aOR) = 1.58 (1.22, 2.05), P = 0.0006 and TT aOR = 1.45 (1.01, 2.04), P = 0.04. In contrast, for those over age 60, the CT aOR = 0.91 (0.73, 1.13), P = 0.37 and TT aOR = 0.86 (0.64, 1.16), P = 0.32. The P-value for the age-genotype interaction was 0.004. For the IL1B +3954 C>T polymorphism, compared with the CC genotype, TT showed significant associations in former smokers and in men but tests of interaction were not significant (P(smoking) = 0.24, P(gender) = 0.17). No interactions were observed for FAS -1377 G>A and BAT3 Ser625Pro polymorphisms. Our findings indicate that age and smoking may modify the association of the FASLG -844 and IL1B + 3954 SNPs with the risk of NSCLC. 18757527 59 85 non-small cell lung cancer Disease D002289 18757527 37 43 cancer Disease D009369 18757527 178 189 lung cancer Disease D008175 18757527 231 236 FASLG Gene 356 18757527 258 262 IL1B Gene 3553 18757527 299 303 BAT3 Gene 7917 18757527 373 399 non-small cell lung cancer Disease D002289 18757527 401 406 NSCLC Disease D002289 18757527 501 506 NSCLC Disease D002289 18757527 661 682 subjects under age 60 Environment 356-D002289 18757527 688 693 FASLG Gene 356 18757527 803 808 NSCLC Disease D002289 18757527 927 944 those over age 60 Environment 356-D002289 18757527 1093 1097 IL1B Gene 3553 18757527 1191 1205 former smokers Environment 3553-D002289 18757527 1213 1216 men Environment 3553-D002289 18757527 1354 1358 BAT3 Gene 7917 18757527 1411 1414 age Environment 356-D002289 18757527 1419 1426 smoking Environment 356-D002289 18757527 1461 1466 FASLG Gene 356 18757527 1476 1480 IL1B Gene 3553 18757527 1510 1515 NSCLC Disease D002289 20605201|t|Gene-environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study. 20605201|t|BACKGROUND: Information is scarce about the combined effects on breast cancer incidence of low-penetrance genetic susceptibility polymorphisms and environmental factors (reproductive, behavioural, and anthropometric risk factors for breast cancer). To test for evidence of gene-environment interactions, we compared genotypic relative risks for breast cancer across the other risk factors in a large UK prospective study. METHODS: We tested gene-environment interactions in 7610 women who developed breast cancer and 10 196 controls without the disease, studying the effects of 12 polymorphisms (FGFR2-rs2981582, TNRC9-rs3803662, 2q35-rs13387042, MAP3K1-rs889312, 8q24-rs13281615, 2p-rs4666451, 5p12-rs981782, CASP8-rs1045485, LSP1-rs3817198, 5q-rs30099, TGFB1-rs1982073, and ATM-rs1800054) in relation to prospectively collected information about ten established environmental risk factors (age at menarche, parity, age at first birth, breastfeeding, menopausal status, age at menopause, use of hormone replacement therapy, body-mass index, height, and alcohol consumption). FINDINGS: After allowance for multiple testing none of the 120 comparisons yielded significant evidence of a gene-environment interaction. By contrast with previous suggestions, there was little evidence that the genotypic relative risks were affected by use of hormone replacement therapy, either overall or for oestrogen-receptor-positive disease. Only one of the 12 polymorphisms was correlated with any of the ten other risk factors: carriers of the high-risk C allele of MAP3K1-rs889312 were significantly shorter than non-carriers (mean height 162.4 cm [95% CI 162.1-162.7] vs 163.1 cm [162.9-163.2]; p=0.01 after allowance for multiple testing). INTERPRETATION: Risks of breast cancer associated with low-penetrance susceptibility polymorphisms do not vary significantly with these ten established environmental risk factors. FUNDING: Cancer Research UK and the UK Medical Research Council. 20605201 49 62 breast cancer Disease D001943 20605201 64 77 breast cancer Disease D001943 20605201 106 113 genetic Disease 1 20605201 233 246 breast cancer Disease D001943 20605201 345 358 breast cancer Disease D001943 20605201 499 512 breast cancer Disease D001943 20605201 596 601 FGFR2 Gene 2263 20605201 613 618 TNRC9 Gene 27324 20605201 647 653 MAP3K1 Gene 4214 20605201 710 715 CASP8 Gene 841 20605201 727 731 LSP1 Gene 4046 20605201 755 760 TGFB1 Gene 7040 20605201 1331 1365 use of hormone replacement therapy Environment 4214-D001943 20605201 1389 1424 oestrogen-receptor-positive disease Environment 4214-D001943 20605201 1552 1558 MAP3K1 Gene 4214 20605201 1754 1767 breast cancer Disease D001943 20605201 1918 1924 Cancer Disease D009369 16510609|t|XRCC1 genotype and breast cancer: functional studies and epidemiologic data show interactions between XRCC1 codon 280 His and smoking. 16510609|t|Tobacco smoke produces oxidative and alkylative DNA damage that necessitates repair by base excision repair coordinated by X-ray cross-complementing gene 1 (XRCC1). We investigated whether polymorphisms in XRCC1 alter DNA repair capacity and modify breast cancer risk associated with smoking. To show the functionality of the 280His variant, we evaluated single-strand break (SSB) repair capacity of isogenic Chinese hamster ovary cells expressing human forms of XRCC1 after exposure to hydrogen peroxide (H(2)O(2)), methyl methanesulfonate (MMS), or camptothecin by monitoring NAD(P)H. We used data from the Carolina Breast Cancer Study (CBCS), a population-based, case-control study that included 2,077 cases (786 African Americans and 1,281 Whites) and 1,818 controls (681 African Americans and 1,137 Whites), to examine associations among XRCC1 codon 194, 280, and 399 genotypes, breast cancer, and smoking. Odds ratios and 95% confidence intervals (95% CI) were calculated by unconditional logistic regression. Only cells expressing the 280His protein accumulated SSB, indicated by NAD(P)H depletion, from both H(2)O(2) and MMS exposures. In the CBCS, positive associations were observed between breast cancer and smoking dose for participants with XRCC1 codon 194 Arg/Arg (P(trend) = 0.046), 399 Arg/Arg (P(trend) = 0.012), and 280 His/His or His/Arg (P(trend) = 0.047) genotypes. The 280His allele was in strong linkage disequilibrium with 194Arg (Lewontin's D' = 1.0) and 399Arg (D' = 1.0). These data suggest that less common, functional polymorphisms may lie within common haplotypes and drive gene-environment interactions. 16510609 0 5 XRCC1 Gene 7515 16510609 19 32 breast cancer Disease D001943 16510609 102 107 XRCC1 Gene 7515 16510609 126 133 smoking Environment 7515-D001943 16510609 123 155 X-ray cross-complementing gene 1 Gene 7515 16510609 157 162 XRCC1 Gene 7515 16510609 206 211 XRCC1 Gene 7515 16510609 249 262 breast cancer Disease D001943 16510609 463 468 XRCC1 Gene 7515 16510609 843 848 XRCC1 Gene 7515 16510609 884 897 breast cancer Disease D001943 16510609 1201 1214 breast cancer Disease D001943 16510609 1219 1231 smoking dose Environment 7515-D001943 16510609 1254 1259 XRCC1 Gene 7515 15598760|t|Polymorphism in the DNA repair gene XPD, polycyclic aromatic hydrocarbon-DNA adducts, cigarette smoking, and breast cancer risk. 15598760|t|DNA repair is essential to an individual's ability to respond to damage caused by environmental carcinogens. Alterations in DNA repair genes may affect cancer risk by influencing individual susceptibility to environmental exposures. XPD, a gene involved in nucleotide excision repair, may influence individual DNA repair capacity particularly of bulky adducts. Using a population-based breast cancer case-control study that was specifically conducted to examine markers of environmental exposures, such as polycyclic aromatic hydrocarbons (PAH), on Long Island, NY, we examined whether XPD genotype modified the associations among PAH-DNA adducts, cigarette smoking, and breast cancer risk. Specifically, we examined the XPD polymorphism at exon 23, position 751 in 1,053 breast cancer cases and 1,102 population-based controls. The presence of at least one variant allele (Lys/Gln or Gln/Gln) was associated with a 20% increase in risk of breast cancer [odds ratio (OR), 1.21; 95% confidence interval (95% CI), 1.01-1.44]. The increase in risk for homozygosity of the variant allele (Gln/Gln) seemed limited to those with PAH-DNA adduct levels above the median(OR, 1.61; 95% CI, 0.99-2.63 for adducts above the median versus OR, 1.05; 95% CI, 0.64-1.74 for adductsbelow the median), although the multiplicative interaction was not statistically significant. The increasein risk for homozygosity of the variant allele (Gln/Gln) was only seen among current smokers (OR, 1.97; 95% CI, 1.02-3.81 for current smokers versus OR, 0.87; 95% CI, 0.57-1.32 for never smokers); the multiplicative interaction was statistically significant. Overall, this study suggests that those individuals with this polymorphism in the XPD gene may face an increased risk of breast cancer from PAH-DNA adducts and cigarette smoking. 15598760 36 39 XPD Gene 2068 15598760 109 122 breast cancer Disease D001943 15598760 152 158 cancer Disease D009369 15598760 233 236 XPD Gene 2068 15598760 386 399 breast cancer Disease D001943 15598760 586 589 XPD Gene 2068 15598760 671 684 breast cancer Disease D001943 15598760 721 724 XPD Gene 2068 15598760 772 785 breast cancer Disease D001943 15598760 940 953 breast cancer Disease D001943 15598760 1448 1463 current smokers Environment 2068-D001943 15598760 1497 1512 current smokers Environment 2068-D001943 15598760 1712 1715 XPD Gene 2068 15598760 1751 1764 breast cancer Disease D001943 15598760 1790 1807 cigarette smoking Environment 2068-D001943 15770010|t|Genetic variants in the UGT1A6 enzyme, aspirin use, and the risk of colorectal adenoma. 15770010|t|Genetic variation in the uridine diphosphate glucuronosyltransferase 1A6 (UGT1A6) enzyme is associated with impaired metabolism of aspirin. To determine whether polymorphisms in the UGT1A6 enzyme modulate the protective benefit of regular aspirin use on colorectal adenoma, we conducted a prospective, nested case-control study of 1062 women who provided blood specimens and detailed data on aspirin use before undergoing lower endoscopy. All statistical tests were two sided. Although UGT1A6 genotype was not associated with overall adenoma risk (multivariable odds ratio [OR] = 1.10, 95% confidence interval [CI] = 0.85 to 1.41), functional variant genotypes statistically significantly modified the effect of aspirin on adenoma (P(interaction) = .02). Among the 616 women with variant genotypes, regular use of aspirin (two or more standard tablets per week) was associated with a decreased risk of adenoma (multivariable OR for adenoma = 0.66 [95% CI = 0.45 to 0.95], OR = 0.63 [95% CI = 0.43 to 0.91] for 0.5-7 standard tablets per week and OR = 0.41 [95% CI = 0.24 to 0.71] for more than 7 tablets per week; P(trend) = .001). In contrast, among women with wild-type genotypes, regular aspirin use was not associated with a reduced risk nor did they obtain any additional benefit with higher doses (P(trend) = .50). These results were consistent among women with advanced adenomas (P(interaction) = .003). Thus, functional polymorphisms in the UGT1A6 enzyme statistically significantly modify the effect of aspirin on colorectal neoplasia, and certain subsets of the population, defined by genotype, may obtain differential benefit from aspirin chemoprevention. 15770010 24 30 UGT1A6 Gene 54578 15770010 68 86 colorectal adenoma Disease 1 15770010 25 72 uridine diphosphate glucuronosyltransferase 1A6 Gene 54578 15770010 74 80 UGT1A6 Gene 54578 15770010 182 188 UGT1A6 Gene 54578 15770010 254 272 colorectal adenoma Disease 1 15770010 486 492 UGT1A6 Gene 54578 15770010 534 541 adenoma Disease D000236 15770010 723 730 adenoma Disease D000236 15770010 799 861 regular use of aspirin (two or more standard tablets per week) Environment 54578-1 15770010 902 909 adenoma Disease D000236 15770010 932 939 adenoma Disease D000236 15770010 1377 1385 adenomas Disease D000236 15770010 1449 1455 UGT1A6 Gene 54578 15770010 1512 1519 aspirin Environment 54578-1 15770010 1523 1543 colorectal neoplasia Disease D015179 16458264|t|Brain-derived neurotrophic factor-5-HTTLPR gene interactions and environmental modifiers of depression in children. 16458264|t|BACKGROUND: Child abuse and genotype interact to contribute to risk for depression in children. This study examined gene-by-gene and gene-by-environment interactions. METHODS: The study included 196 children: 109 maltreated and 87 nonmaltreated comparison subjects. Measures of psychiatric symptomatology and social supports were obtained using standard research instruments, and serotonin transporter (5-HTTLPR) (locus SLC6A4) and brain-derived neurotrophic factor (BDNF) (variant val66met) genotypes were obtained from saliva-derived DNA specimens. Population structure was controlled by means of ancestral proportion scores computed based on genotypes of ancestry informative markers in the entire sample. RESULTS: There was a significant three-way interaction between BDNF genotype, 5-HTTLPR, and maltreatment history in predicting depression. Children with the met allele of the BDNF gene and two short alleles of 5-HTTLPR had the highest depression scores, but the vulnerability associated with these two genotypes was only evident in the maltreated children. A significant four-way interaction also emerged, with social supports found to further moderate risk for depression. CONCLUSIONS: To the best of our knowledge, this is the first investigation to demonstrate a gene-by-gene interaction conveying vulnerability to depression. The current data also show a protective effect of social supports in ameliorating genetic and environmental risk for psychopathology. 16458264 0 33 Brain-derived neurotrophic factor Gene 627 16458264 34 42 5-HTTLPR Gene 6532 16458264 92 102 depression Disease D003866 16458264 72 82 depression Disease D003866 16458264 278 289 psychiatric Disease D001523 16458264 403 411 5-HTTLPR Gene 6532 16458264 420 426 SLC6A4 Gene 6532 16458264 432 465 brain-derived neurotrophic factor Gene 627 16458264 467 471 BDNF Gene 627 16458264 772 776 BDNF Gene 627 16458264 787 795 5-HTTLPR Gene 6532 16458264 801 821 maltreatment history Environment 6532-D003866 16458264 801 821 maltreatment history Environment 627-D003866 16458264 835 845 depression Disease D003866 16458264 883 887 BDNF Gene 627 16458264 918 926 5-HTTLPR Gene 6532 16458264 943 953 depression Disease D003866 16458264 1040 1063 the maltreated children Environment 6532-D003866 16458264 1040 1063 the maltreated children Environment 627-D003866 16458264 1119 1134 social supports Environment 6532-D003866 16458264 1119 1134 social supports Environment 627-D003866 16458264 1170 1180 depression Disease D003866 16458264 1326 1336 depression Disease D003866 16458264 1388 1403 social supports Environment 6532-D003866 16458264 1388 1403 social supports Environment 627-D003866 19623649|t|TP53 Arg72Pro polymorphism and lung cancer risk: a meta-analysis. 19623649|t|No clear consensus has been reached on the TP53 Arg72Pro polymorphism (G12139C) and lung cancer risk. Thus, a meta-analysis was conducted to summarize the possible association. There was no statistical association between 12139C (Pro allele) and lung cancer risk in Caucasians compared with 12139G allele. However, the association was observed in all subjects (9,387 patients and 9,922 controls, p=0.04, OR=1.08, 95% CI 1.00-1.17), as well as in Asians (p=0.0004, OR=1.14, 95% CI 1.06-1.22). The association was also found in Asians under recessive genetic model (p<0.00001, OR=1.37, 95% CI 1.20-1.57) and homozygote comparison (CC vs. GG) (p<0.0001, OR=1.34, 95% CI 1.16-1.56). 12139C allele might increase the lung adenocarcinoma risk compared with 12139G allele (p=0.01, OR=1.11, 95% CI 1.02-1.21), and the effect was also found under recessive genetic model (p=0.003, OR=1.28, 95% CI 1.09-1.50) and homozygote comparison (CC vs. GG) (p=0.007, OR=1.28, 95% CI 1.07-1.52). There was an elevated association between the 12139C and the stage I lung cancer under dominant genetic model (p=0.04, OR=1.48, 95% CI 1.02-2.16), but no association was observed in other stages. No association of smoking was found between 12139C allele and lung cancer under recessive genetic model. Our result indicated that 12139C might increase the risk of lung cancer under recessive genetic model in adenocarcinoma, in Asians, and in lung cancer stage I. More studies stratified for lung cancer stage-genotyping interaction should be performed to clarify the role of TP53 Arg72Pro polymorphism in the development of lung cancer. 19623649 0 4 TP53 Gene 7157 19623649 31 42 lung cancer Disease D008175 19623649 43 47 TP53 Gene 7157 19623649 84 95 lung cancer Disease D008175 19623649 246 257 lung cancer Disease D008175 19623649 446 452 Asians Environment 7157-D008175 19623649 526 532 Asians Environment 7157-D008175 19623649 712 731 lung adenocarcinoma Disease C538231 19623649 1032 1055 the stage I lung cancer Environment 7157-D008175 19623649 1044 1055 lung cancer Disease D008175 19623649 1233 1244 lung cancer Disease D008175 19623649 1336 1347 lung cancer Disease D008175 19623649 1381 1395 adenocarcinoma Disease D000230 19623649 1381 1395 adenocarcinoma Environment 7157-D008175 19623649 1400 1406 Asians Environment 7157-D008175 19623649 1415 1426 lung cancer Disease D008175 19623649 1415 1434 lung cancer stage I Environment 7157-D008175 19623649 1464 1475 lung cancer Disease D008175 19623649 1548 1552 TP53 Gene 7157 19623649 1597 1608 lung cancer Disease D008175 19846565|t|Genetic variation in the progesterone receptor and metabolism pathways and hormone therapy in relation to breast cancer risk. 19846565|t|The relevance of progesterone to breast carcinogenesis is highlighted by evidence indicating that use of combined estrogen-progesterone therapy (EPT) is more strongly related to breast cancer risk than is use of unopposed estrogen therapy. However, few investigators have assessed how genetic variation in progesterone-related genes modifies the effect of EPT on risk. In an analysis combining data from 2 population-based case-control studies of postmenopausal breast cancer (1,296 cases and 1,055 controls) conducted in Washington State in 1997-1999 and 2000-2004, the authors evaluated how 51 single nucleotide polymorphisms in 7 progesterone-related genes (AKR1C1, AKR1C2, AKR1C3, CYP3A4, SRD5A1, SRD5A2, and PGR) influenced breast cancer risk. There was no appreciable association with breast cancer risk overall for any single nucleotide polymorphism. For rs2854482 in AKR1C2, carrying 1 or 2 A alleles was associated with a 2.0-fold increased breast cancer risk in EPT users (95% confidence interval: 1.0, 4.0) but not in never users (P(heterogeneity) = 0.03). For rs12387 in AKR1C3, the presence of 1 or 2 G alleles was associated with a 1.5-fold increased risk among EPT users (95% confidence interval: 1.1, 2.2) but not in never users (P(heterogeneity) = 0.02). Interpretation of these subgroup associations must await the results of similar studies conducted in other populations. 19846565 25 46 progesterone receptor Gene 5241 19846565 106 119 breast cancer Disease D001943 19846565 40 54 carcinogenesis Disease D063646 19846565 178 191 breast cancer Disease D001943 19846565 462 475 breast cancer Disease D001943 19846565 661 667 AKR1C1 Gene 1645 19846565 669 675 AKR1C2 Gene 1646 19846565 677 683 AKR1C3 Gene 8644 19846565 685 691 CYP3A4 Gene 1576 19846565 693 699 SRD5A1 Gene 6715 19846565 701 707 SRD5A2 Gene 6716 19846565 713 716 PGR Gene 5241 19846565 729 742 breast cancer Disease D001943 19846565 791 804 breast cancer Disease D001943 19846565 875 881 AKR1C2 Gene 1646 19846565 950 963 breast cancer Disease D001943 19846565 972 981 EPT users Environment 1646-D001943 19846565 1083 1089 AKR1C3 Gene 8644 19846565 1176 1185 EPT users Environment 8644-D001943 20176930|t|Computational identification of gene-social environment interaction at the human IL6 locus. 20176930|t|To identify genetic factors that interact with social environments to impact human health, we used a bioinformatic strategy that couples expression array-based detection of environmentally responsive transcription factors with in silico discovery of regulatory polymorphisms to predict genetic loci that modulate transcriptional responses to stressful environments. Tests of one predicted interaction locus in the human IL6 promoter (SNP rs1800795) verified that it modulates transcriptional response to beta-adrenergic activation of the GATA1 transcription factor in vitro. In vivo validation studies confirmed links between adverse social conditions and increased transcription of GATA1 target genes in primary neural, immune, and cancer cells. Epidemiologic analyses verified the health significance of those molecular interactions by documenting increased 10-year mortality risk associated with late-life depressive symptoms that occurred solely for homozygous carriers of the GATA1-sensitive G allele of rs1800795. Gating of depression-related mortality risk by IL6 genotype pertained only to inflammation-related causes of death and was associated with increased chronic inflammation as indexed by plasma C-reactive protein. Computational modeling of molecular interactions, in vitro biochemical analyses, in vivo animal modeling, and human molecular epidemiologic analyses thus converge in identifying beta-adrenergic activation of GATA1 as a molecular pathway by which social adversity can alter human health risk selectively depending on individual genetic status at the IL6 locus. 20176930 81 84 IL6 Gene 3569 20176930 420 423 IL6 Gene 3569 20176930 538 543 GATA1 Gene 2623 20176930 626 651 adverse social conditions Environment 2623-D003866 20176930 683 688 GATA1 Gene 2623 20176930 733 739 cancer Disease D009369 20176930 909 928 depressive symptoms Disease D003866 20176930 981 986 GATA1 Gene 2623 20176930 1030 1040 depression Disease D003866 20176930 1067 1070 IL6 Gene 3569 20176930 1098 1110 inflammation Disease D007249 20176930 1177 1189 inflammation Disease D007249 20176930 1211 1229 C-reactive protein Gene 1401 20176930 1439 1444 GATA1 Gene 2623 20176930 1580 1583 IL6 Gene 3569 20043206|t|Factors influencing the association between CYP17 T34C polymorphism and the risk of breast cancer: meta-regression and subgroup analysis. 20043206|t|A number of studies have been investigated the association between CYP17 T34C polymorphism and the risk of breast cancer; the results of these studies are inconsistent, however. This fact implies that the effect of CYP17 T34C polymorphism on susceptibility to breast cancer may be modified by other risk factors. In order to provide a more definitive conclusion, a full meta-analysis combining and summarizing 24 studies was first performed. Both traditional method and Bayesian approach were applied. Odds ratio was estimated using a dominant mode of inheritance after a biological justification for the choice of genetic model. The results of homogeneity analysis (H = 1.16, I (2) = 25.4%, and P = 0.127) suggested the presence of heterogeneity across the studies. Thus, random effects models simulated by the DerSimonian-Laird method were employed. The capability of a Bayesian approach was highlighted in the estimation of a pooled odds ratio and 95% confidence interval. The results of meta-analysis (OR = 1.001, CI = 0.832-1.208) suggest no significant association in the combined populations. Furthermore, Bayesian meta-regression and subgroup analysis were conducted to investigate the sources of heterogeneity. The risk factors evaluated in the study were menopausal status, ethnicity, age at menarche, age at first birth, parity, use of oral contraceptives, body mass index (BMI), and use of hormone repair therapy (HRT). After these population stratifications, there was evidence indicating that a possible impact of menopausal status, age at menarche, and BMI on the association between CYP17 T34C polymorphism and the risk of breast cancer. 20043206 44 49 CYP17 Gene 1586 20043206 84 97 breast cancer Disease D001943 20043206 67 72 CYP17 Gene 1586 20043206 107 120 breast cancer Disease D001943 20043206 215 220 CYP17 Gene 1586 20043206 260 273 breast cancer Disease D001943 20043206 1528 1545 menopausal status Environment 1586-D001943 20043206 1547 1562 age at menarche Environment 1586-D001943 20043206 1568 1571 BMI Environment 1586-D001943 20043206 1599 1604 CYP17 Gene 1586 20043206 1639 1652 breast cancer Disease D001943 19843673|t|Sequence variant on 3q28 and urinary bladder cancer risk: findings from the Los Angeles-Shanghai bladder case-control study. 19843673|t|Recently, the first genome-wide association study of bladder cancer identified an association of genome-wide significance between single nucleotide polymorphism (SNP) rs715021 and urinary bladder cancer risk among European individuals. This SNP is in a haplotype block in linkage disequilibrium with the TP63 gene. We investigated the role of this SNP among 1,042 cases and 1,123 controls among non-Latino whites in Los Angeles County, CA and among Chinese in Shanghai, China. We confirmed an association between the A allele and bladder cancer risk [log-additive per A allele odds ratios (OR), 1.24; and 95% confidence intervals (95% CI), 1.02-1.52; P = 0.032] in Los Angeles County and a similar association in Shanghai (log-additive per A allele OR, 1.21; 95% CI, 0.98-1.49; P = 0.080). These estimates did not differ by study site, smoking status, or gender. However, the effects were greater in older individuals. Analysis within non-Latino whites, for whom we had histologic results, revealed that this association was restricted to low-risk tumors (OR, 1.49; 95% CI, 1.17-1.92; P = 0.002) and absent among high-risk tumors (OR, 1.03; 95% CI, 0.80-1.33; P = 0.790; heterogeneity, P = 0.019). A positive association (OR, 1.56; 95% CI, 0.93-2.62; P = 0.089) was only observed among high-risk tumors from individuals older than 56 years old (interaction, P = 0.045). Our results suggest that a TP63 gene variant may increase susceptibility for the development of urinary bladder tumors with low risk of progression. 19843673 29 51 urinary bladder cancer Disease D001749 19843673 53 67 bladder cancer Disease D001749 19843673 180 202 urinary bladder cancer Disease D001749 19843673 304 308 TP63 Gene 8626 19843673 530 544 bladder cancer Disease D001749 19843673 900 917 older individuals Environment 8626-D001749 19843673 1048 1054 tumors Disease D009369 19843673 1123 1129 tumors Disease D009369 19843673 1296 1302 tumors Disease D009369 19843673 1308 1343 individuals older than 56 years old Environment 8626-D001749 19843673 1397 1401 TP63 Gene 8626 19843673 1474 1488 bladder tumors Disease D001749 20403997|t|Genetic variation in 3-hydroxy-3-methylglutaryl CoA reductase modifies the chemopreventive activity of statins for colorectal cancer. 20403997|t|Genetic variation in 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR), the rate-limiting enzyme in cholesterol synthesis, modifies the effect of statins on serum cholesterol levels. Long-term use of statins is associated with a reduced risk of colorectal cancer (CRC) in some, but not all, studies. We genotyped variants in 40 candidate genes important for cholesterol synthesis and metabolism in a population-based case-control study of CRC involving 2,138 incident cases and 2,049 population-based controls. We identified a single-nucleotide polymorphism in the HMGCR gene that significantly modified the protective association between statins and CRC risk. Compared with nonusers, the unadjusted odds ratio of CRC among statin users with the A/A genotype of rs12654264 in HMGCR was 0.3 (95% confidence interval, 0.18-0.51) and among statin users with the T/T genotype was 0.66 (95% confidence interval, 0.41-1.06; P-interaction = 0.0012). This genetic variant (A/A genotype of rs12654264) also was associated with lower serum levels of low-density lipoprotein among all cases and controls. In colon cancer cell lines, the reduction in cholesterol levels after statin treatment was substantially stronger in cells carrying the A/A genotype, and this difference was related to alternative splicing involving the HMGCR statin-binding domain. We anticipate that these data may advance the development of personalized statin use for reducing the risk of cancer as well as cardiovascular disease among the approximately 25 million people currently using statins worldwide. 20403997 21 61 3-hydroxy-3-methylglutaryl CoA reductase Gene 3156 20403997 71 110 the chemopreventive activity of statins Environment 3156-D015179 20403997 115 132 colorectal cancer Disease D015179 20403997 21 61 3-hydroxy-3-methylglutaryl CoA reductase Gene 3156 20403997 63 68 HMGCR Gene 3156 20403997 244 261 colorectal cancer Disease D015179 20403997 263 266 CRC Disease D015179 20403997 438 441 CRC Disease D015179 20403997 564 569 HMGCR Gene 3156 20403997 638 645 statins Environment 3156-D015179 20403997 650 653 CRC Disease D015179 20403997 713 716 CRC Disease D015179 20403997 723 735 statin users Environment 3156-D015179 20403997 775 780 HMGCR Gene 3156 20403997 836 848 statin users Environment 3156-D015179 20403997 1017 1062 lower serum levels of low-density lipoprotein Environment 3156-D015179 20403997 1096 1108 colon cancer Disease D003110 20403997 1121 1179 the reduction in cholesterol levels after statin treatment Environment 3156-D015179 20403997 1313 1318 HMGCR Gene 3156 20403997 1452 1458 cancer Disease D009369 20403997 1470 1492 cardiovascular disease Disease D002318 20029939|t|Polymorphisms in CRHR1 and the serotonin transporter loci: gene x gene x environment interactions on depressive symptoms. 20029939|t|Gene x environment (G x E) interactions mediating depressive symptoms have been separately identified in the stress-sensitive serotonergic (5-HTTLPR) and corticotropin-releasing hormone (CRHR1) systems. Our objective was to examine whether the effects of child abuse are moderated by gene x gene (G x G) interactions between CRHR1 and 5-HTTLPR polymorphisms. We used an association study examining G x G x E interactions of CRHR1 and 5-HTTLPR polymorphisms and measures of child abuse on adult depressive symptomatology. The participant population (N = 1,392) was African-American, of low socioeconomic status (60% with <$1,000/month family income), and with high rates of childhood and lifetime trauma. Depressive symptoms were measured with Beck Depression Inventory (BDI) and history of Major Depression by Structure Clinical Interview based on DSM-IV (SCID). We first replicated an interaction of child abuse and 5-HTTLPR on lifetime SCID diagnosis of major depression in a subsample (N = 236) of the study population-the largest African-American 5-HTTLPR cohort reported to date. We then extended our previously reported interaction with both a CRHR1 SNP (rs110402) and TCA haplotype interacting with child abuse to predict current symptoms (N = 1,059; P = 0.0089). We found that the 5-HTTLPR S allele interacted with CRHR1 haplotypes and child abuse to predict current depressive symptoms (N = 856, P = 0.016). These data suggest that G x E interactions predictive of depressive symptoms may be differentially sensitive to levels of childhood trauma, and the effects of child abuse are moderated by genetic variation at both the CRHR1 and 5-HTTLPR loci and by their G x G interaction. 20029939 17 22 CRHR1 Gene 1394 20029939 31 52 serotonin transporter Gene 6532 20029939 101 120 depressive symptoms Disease D003866 20029939 50 69 depressive symptoms Disease D003866 20029939 140 148 5-HTTLPR Gene 6532 20029939 154 185 corticotropin-releasing hormone Gene 1392 20029939 187 192 CRHR1 Gene 1394 20029939 325 330 CRHR1 Gene 1394 20029939 335 343 5-HTTLPR Gene 6532 20029939 424 429 CRHR1 Gene 1394 20029939 434 442 5-HTTLPR Gene 6532 20029939 494 504 depressive Disease D003866 20029939 696 702 trauma Disease D014947 20029939 704 723 Depressive symptoms Disease D003866 20029939 748 758 Depression Disease D003866 20029939 790 806 Major Depression Disease D003865 20029939 917 925 5-HTTLPR Gene 6532 20029939 956 972 major depression Disease D003865 20029939 1051 1059 5-HTTLPR Gene 6532 20029939 1150 1155 CRHR1 Gene 1394 20029939 1289 1297 5-HTTLPR Gene 6532 20029939 1323 1328 CRHR1 Gene 1394 20029939 1344 1355 child abuse Environment 6532-D003866 20029939 1344 1355 child abuse Environment 1394-D003866 20029939 1375 1394 depressive symptoms Disease D003866 20029939 1474 1493 depressive symptoms Disease D003866 20029939 1529 1555 levels of childhood trauma Environment 6532-D003866 20029939 1529 1555 levels of childhood trauma Environment 1394-D003866 20029939 1549 1555 trauma Disease D014947 20029939 1576 1587 child abuse Environment 6532-D003866 20029939 1576 1587 child abuse Environment 1394-D003866 20029939 1635 1640 CRHR1 Gene 1394 20029939 1645 1653 5-HTTLPR Gene 6532 15252846|t|Dietary calcium, vitamin D, VDR genotypes and colorectal cancer. 15252846|t|The vitamin D receptor (VDR) may importantly modulate risk of colorectal cancer either independently or in conjunction with calcium and vitamin D intake. We evaluate the association between calcium, vitamin D, dairy products, and VDR polymorphisms in 2 case-control studies of colon and rectal cancer (n = 2,306 cases and 2,749 controls). Dietary intake was evaluated using a detailed diet history questionnaire. Two VDR polymorphisms were evaluated: an intron 8 Bsm 1 polymorphism and a 3' untranslated region poly-A length polymorphism (designated S for short and L for long). The SS genotype reduced risk of colorectal cancer for men (odds ratio [OR] = 0.71; 95% confidence interval [CI] = 0.55-0.92). High levels of calcium intake reduced risk of rectal cancer in women (OR = 0.39; 95% CI = 0.24-0.64) but were not associated with rectal cancer in men (OR = 1.02; 95% CI = 0.66-1.56). Similar reduced rectal cancer risk among women was observed at high levels of vitamin D (OR = 0.52; 95% CI = 0.32-0.85) and low-fat dairy products (OR = 0.61; 95% CI = 0.39-0.94). High levels of sunshine exposure reduced risk of rectal cancer among those diagnosed when <60 years of age (OR = 0.62, 95% CI = 0.42-0.93). Examination of calcium in conjunction with VDR genotype showed that a significant 40% reduction in risk of rectal cancer was observed for the SS or BB VDR genotypes when calcium intake was low (p interaction = 0.01 for calcium interaction). For colon cancer, high levels of dietary intake of calcium, vitamin D, and low-fat dairy products reduced risk of cancer for the SS or BB VDR genotypes, although the p for interaction was not statistically significant. These data support previous observations that high levels of calcium and vitamin D reduce risk of rectal cancer and provide support for a weak protective effect for the SS and BB VDR genotypes. The risk associated with VDR genotype seems to depend upon the level of dietary calcium and vitamin D and tumor site. 15252846 28 31 VDR Gene 7421 15252846 46 63 colorectal cancer Disease D015179 15252846 4 22 vitamin D receptor Gene 7421 15252846 24 27 VDR Gene 7421 15252846 62 79 colorectal cancer Disease D015179 15252846 230 233 VDR Gene 7421 15252846 294 300 cancer Disease D009369 15252846 417 420 VDR Gene 7421 15252846 611 628 colorectal cancer Disease D015179 15252846 758 764 cancer Disease D009369 15252846 842 848 cancer Disease D009369 15252846 912 918 cancer Disease D009369 15252846 1125 1131 cancer Disease D009369 15252846 1252 1255 VDR Gene 7421 15252846 1323 1329 cancer Disease D009369 15252846 1360 1363 VDR Gene 7421 15252846 1379 1401 calcium intake was low Environment 7421-D009369 15252846 1454 1466 colon cancer Disease D003110 15252846 1564 1570 cancer Disease D009369 15252846 1588 1591 VDR Gene 7421 15252846 1715 1751 high levels of calcium and vitamin D Environment 7421-D009369 15252846 1774 1780 cancer Disease D009369 15252846 1848 1851 VDR Gene 7421 15252846 1888 1891 VDR Gene 7421 15252846 1922 1964 the level of dietary calcium and vitamin D Environment 7421-D009369 15252846 1969 1974 tumor Disease D009369 22573796|t|Multistage analysis of variants in the inflammation pathway and lung cancer risk in smokers. 22573796|t|BACKGROUND: Tobacco-induced lung cancer is characterized by a deregulated inflammatory microenvironment. Variants in multiple genes in inflammation pathways may contribute to risk of lung cancer. METHODS: We therefore conducted a three-stage comprehensive pathway analysis (discovery, replication, and meta-analysis) of inflammation gene variants in ever-smoking lung cancer cases and controls. A discovery set (1,096 cases and 727 controls) and an independent and nonoverlapping internal replication set (1,154 cases and 1,137 controls) were derived from an ongoing case-control study. For discovery, we used an iSelect BeadChip to interrogate a comprehensive panel of 11,737 inflammation pathway single-nucleotide polymorphisms (SNP) and selected nominally significant (P < 0.05) SNPs for internal replication. RESULTS: There were six SNPs that achieved statistical significance (P < 0.05) in the internal replication data set with concordant risk estimates for former smokers and five concordant and replicated SNPs in current smokers. Replicated hits were further tested in a subsequent meta-analysis using external data derived from two published genome-wide association studies (GWAS) and a case-control study. Two of these variants (a BCL2L14 SNP in former smokers and an SNP in IL2RB in current smokers) were further validated. In risk score analyses, there was a 26% increase in risk with each additional adverse allele when we combined the genotyped SNP and the most significant imputed SNP in IL2RB in current smokers and a 36% similar increase in risk for former smokers associated with genotyped and imputed BCL2L14 SNPs. CONCLUSIONS/IMPACT: Before they can be applied for risk prediction efforts, these SNPs should be subject to further external replication and more extensive fine mapping studies. 22573796 39 51 inflammation Disease D007249 22573796 64 75 lung cancer Disease D008175 22573796 28 39 lung cancer Disease D008175 22573796 135 147 inflammation Disease D007249 22573796 183 194 lung cancer Disease D008175 22573796 320 332 inflammation Disease D007249 22573796 363 374 lung cancer Disease D008175 22573796 677 689 inflammation Disease D007249 22573796 1242 1249 BCL2L14 Gene 79370 22573796 1286 1291 IL2RB Gene 3560 22573796 1504 1509 IL2RB Gene 3560 22573796 1513 1528 current smokers Environment 79370-D008175 22573796 1568 1582 former smokers Environment 3560-D008175 22573796 1621 1628 BCL2L14 Gene 79370 19467856|t|Association between manganese superoxide dismutase (MnSOD) Val-9Ala polymorphism and cancer risk - A meta-analysis. 19467856|t|A growing body of evidence suggests that reactive oxygen species (ROS) play an important role in human cancers. Manganese superoxide dismutase (MnSOD) is the major antioxidant in the mitochondria, catalysing the dismutation of superoxide radicals to form hydrogen peroxide. Since the identification of a well-characterised functional polymorphism, Val-9Ala of MnSOD, a number of molecular epidemiological studies have evaluated the association between Val-9Ala and cancer risk. However, the results remain conflicting rather than conclusive. This meta-analysis on 15,320 cancer cases and 19,534 controls from 34 published case-control studies shows no significant overall main effect of MnSOD Val-9Ala on cancer risk. However, we found that the MnSOD 9Ala allele was associated with an increased prostate cancer risk (Val/Ala versus Val/Val: odds ratio (OR)=1.1; 95% confidence intervals (CI): 1.0-1.3; Ala/Ala versus Val/Val: OR=1.3; 95% CI: 1.0-1.6; Val/Ala+Ala/Ala versus Val/Val: OR=1.2; 95% CI, 1.0-1.3). In addition, we found that the MnSOD Ala-9Ala genotype contributed to an increased breast cancer risk in premenopausal women who had low consumption of antioxidants (Ala/Ala versus Val/Ala+Val/Val: OR=2.6, 95% CI: 1.0-6.4 with low vitamin C consumption; OR=2.1, 95%CI: 1.3-3.4 with low vitamin E consumption and OR=2.9, 95%CI: 1.5-5.7 with low carotenoid consumption). These results suggest that the MnSOD Val-9Ala polymorphism may contribute to cancer development through a disturbed antioxidant balance. 19467856 20 50 manganese superoxide dismutase Gene 6648 19467856 52 57 MnSOD Gene 6648 19467856 85 91 cancer Disease D009369 19467856 103 110 cancers Disease D009369 19467856 112 142 Manganese superoxide dismutase Gene 6648 19467856 144 149 MnSOD Gene 6648 19467856 360 365 MnSOD Gene 6648 19467856 465 471 cancer Disease D009369 19467856 571 577 cancer Disease D009369 19467856 687 692 MnSOD Gene 6648 19467856 705 711 cancer Disease D009369 19467856 745 750 MnSOD Gene 6648 19467856 796 811 prostate cancer Disease D011471 19467856 1041 1046 MnSOD Gene 6648 19467856 1093 1106 breast cancer Disease D001943 19467856 1143 1174 low consumption of antioxidants Environment 6648-D001943 19467856 1237 1262 low vitamin C consumption Environment 6648-D001943 19467856 1292 1317 low vitamin E consumption Environment 6648-D001943 19467856 1350 1376 low carotenoid consumption Environment 6648-D001943 19467856 1410 1415 MnSOD Gene 6648 19467856 1456 1462 cancer Disease D009369 19467856 1483 1514 a disturbed antioxidant balance Environment 6648-D001943 21068203|t|Genetic variation in the TGF-beta signaling pathway and colon and rectal cancer risk. 21068203|t|BACKGROUND: The TGF-beta signaling pathway is an essential regulator of many cellular process involved in carcinogenesis. Smad proteins are central to the function of TGF-beta signaling. In this study, we evaluated genetic variation in TGFbeta1, TGFbetaR1, Smad1, Smad2, Smad3, and Smad4 and risk of colon and rectal cancer. METHODS: Data are from a large case-control study of colon (n = 1,444 cases, 1,841 controls) and rectal (n = 754 cases, 856 controls) cancer participants with DNA. RESULTS: Both TGFbeta1 rs1800469 and rs4803455 were associated with colon cancer [odds ratio (OR) = 0.65 and 1.43, 95% CI = 0.51-0.84 and 1.18-1.73, respectively) but not rectal cancer. Likewise, 1 of 3 tagSNPs for TGFbetaR1, 2 of the 4 tagSNPs for Smad2, and 4 of 37 Smad3 tagSNPs were associated with colon cancer. Fewer significant associations were observed for rectal cancer, with only 1 tagSNP in Smad2 and 3 tagSNP in Smad3 having 95% CIs excluding 1.0. Several Smad3 tagSNPs were only associated with CpG island methylator phenotype. We observed several statistically significant interactions between genetic variation in the TGF-beta signaling pathway and NFkappaB1, further illustrating its involvement in proposed mechanisms. In addition, we observed statistically significant interaction between TGFbeta1, TGFbetaR1, and Smad3 and cigarette smoking, aspirin use, and estrogen status for both colon and rectal cancers. Variation in TGFbeta1, TGFbetaR1, and Smad3 seemed to influence survival after diagnosis of colon and rectal cancer. CONCLUSIONS: These findings provide further support for genetic variation in the TGF-beta signaling pathway and risk of developing both colon and rectal cancers. IMPACT: Insight into biological pathways is provided. 21068203 25 33 TGF-beta Gene 7040 21068203 66 79 rectal cancer Disease D012004 21068203 16 24 TGF-beta Gene 7040 21068203 106 120 carcinogenesis Disease D063646 21068203 167 175 TGF-beta Gene 7040 21068203 236 244 TGFbeta1 Gene 7040 21068203 257 262 Smad1 Gene 4086 21068203 264 269 Smad2 Gene 4087 21068203 271 276 Smad3 Gene 4088 21068203 282 287 Smad4 Gene 4089 21068203 310 323 rectal cancer Disease D012004 21068203 459 465 cancer Disease D009369 21068203 503 511 TGFbeta1 Gene 7040 21068203 557 569 colon cancer Disease D003110 21068203 660 673 rectal cancer Disease D012004 21068203 738 743 Smad2 Gene 4087 21068203 757 762 Smad3 Gene 4088 21068203 792 804 colon cancer Disease D003110 21068203 855 868 rectal cancer Disease D012004 21068203 892 897 Smad2 Gene 4087 21068203 914 919 Smad3 Gene 4088 21068203 958 963 Smad3 Gene 4088 21068203 1123 1131 TGF-beta Gene 7040 21068203 1297 1305 TGFbeta1 Gene 7040 21068203 1322 1327 Smad3 Gene 4088 21068203 1332 1349 cigarette smoking Environment 7040-D012004 21068203 1332 1349 cigarette smoking Environment 4088-D012004 21068203 1332 1349 cigarette smoking Environment 4088-D003110 21068203 1332 1349 cigarette smoking Environment 7040-D003110 21068203 1351 1362 aspirin use Environment 7040-D012004 21068203 1351 1362 aspirin use Environment 4088-D012004 21068203 1351 1362 aspirin use Environment 4088-D003110 21068203 1351 1362 aspirin use Environment 7040-D003110 21068203 1368 1383 estrogen status Environment 7040-D012004 21068203 1368 1383 estrogen status Environment 4088-D012004 21068203 1368 1383 estrogen status Environment 4088-D003110 21068203 1368 1383 estrogen status Environment 7040-D003110 21068203 1403 1417 rectal cancers Disease D012004 21068203 1432 1440 TGFbeta1 Gene 7040 21068203 1457 1462 Smad3 Gene 4088 21068203 1528 1534 cancer Disease D009369 21068203 1617 1625 TGF-beta Gene 7040 21068203 1682 1696 rectal cancers Disease D012004 19424794|t|Genetic polymorphisms in phase I and phase II enzymes and breast cancer risk associated with menopausal hormone therapy in postmenopausal women. 19424794|t|Recent findings indicate a greater risk of postmenopausal breast cancer with estrogen-progestagen therapy than estrogen monotherapy, and more so for current than past use. Few studies have examined individual genetic susceptibility to the effects of menopausal hormone therapy. We used two population-based case-control studies with 3,155 postmenopausal breast cancer patients and 5,496 controls to evaluate modification of breast cancer risk associated with duration of hormone use by genes involved in hormone metabolism and detoxification. Twenty-eight polymorphisms in eight genes of phase I (CYP1A1, CYP1A2, CYP1B1, CYP2C9, CYP2C19, CYP3A4, CYP3A5, CYP3A7) and nine genes of phase II enzymes (COMT, GSTM1, GSTM3, GSTP1, GSTT1, SULT1A1, UGT1A1, UGT1A6, UGT2B7) were genotyped. The risk associated with duration of use of combined estrogen-progestagen therapy was significantly modified by genetic polymorphisms located in CYP1B1, GSTP1, and GSTT1. In homozygote carriers of the CYP1B1_142_G and the CYP1B1_355 _T variant alleles, adjusted odds ratios (OR) per year of use were 1.06 (95% confidence interval (CI) = 1.02-1.09) and 1.06 (95% CI = 1.03-1.09), respectively, compared with 1.02 (95% CI = 1.01-1.03) in non-carriers of either polymorphism (p(interaction) = 0.01). Carriers of the functional GSTT1 allele and the GSTP1_341_T allele were at significantly higher risks associated with hormone use compared with non-carriers (p(interaction) = 0.0001 and 0.02). CYP1A1_2452_C>A significantly reduced the risk associated with duration of use of estrogen monotherapy (p(interaction) = 0.01). The finding regarding GSTT1 was still statistically significant after corrections for multiple comparisons. Postmenopausal breast cancer risk associated with hormone therapy may be modified by genetically determined variations in phase I and II enzymes involved in steroid hormone metabolism. 19424794 58 71 breast cancer Disease D001943 19424794 58 71 breast cancer Disease D001943 19424794 209 216 genetic Disease 1 19424794 354 367 breast cancer Disease D001943 19424794 424 437 breast cancer Disease D001943 19424794 597 603 CYP1A1 Gene 1543 19424794 605 611 CYP1A2 Gene 1544 19424794 613 619 CYP1B1 Gene 1545 19424794 621 627 CYP2C9 Gene 1559 19424794 629 636 CYP2C19 Gene 1557 19424794 638 644 CYP3A4 Gene 1576 19424794 646 652 CYP3A5 Gene 1577 19424794 654 660 CYP3A7 Gene 1551 19424794 698 702 COMT Gene 1312 19424794 704 709 GSTM1 Gene 2944 19424794 711 716 GSTM3 Gene 2947 19424794 718 723 GSTP1 Gene 2950 19424794 725 730 GSTT1 Gene 2952 19424794 732 739 SULT1A1 Gene 6817 19424794 741 747 UGT1A1 Gene 54658 19424794 749 755 UGT1A6 Gene 54578 19424794 757 763 UGT2B7 Gene 7364 19424794 806 862 duration of use of combined estrogen-progestagen therapy Environment 2950-D001943 19424794 806 862 duration of use of combined estrogen-progestagen therapy Environment 1545-D001943 19424794 806 862 duration of use of combined estrogen-progestagen therapy Environment 2952-D001943 19424794 892 899 genetic Disease 1 19424794 925 931 CYP1B1 Gene 1545 19424794 933 938 GSTP1 Gene 2950 19424794 944 949 GSTT1 Gene 2952 19424794 981 987 CYP1B1 Gene 1545 19424794 1002 1008 CYP1B1 Gene 1545 19424794 1304 1309 GSTT1 Gene 2952 19424794 1325 1330 GSTP1 Gene 2950 19424794 1395 1406 hormone use Environment 2950-D001943 19424794 1395 1406 hormone use Environment 2952-D001943 19424794 1470 1476 CYP1A1 Gene 1543 19424794 1533 1572 duration of use of estrogen monotherapy Environment 1545-D001943 19424794 1620 1625 GSTT1 Gene 2952 19424794 1721 1734 breast cancer Disease D001943 19424794 1756 1771 hormone therapy Environment 2950-D001943 19424794 1756 1771 hormone therapy Environment 1545-D001943 19424794 1756 1771 hormone therapy Environment 2952-D001943 21940907|t|Joint effects of alcohol consumption and polymorphisms in alcohol and oxidative stress metabolism genes on risk of head and neck cancer. 21940907|t|BACKGROUND: Single-nucleotide polymorphisms (SNP) in alcohol metabolism genes are associated with squamous cell carcinoma of the head and neck (SCCHN) and may influence cancer risk in conjunction with alcohol. Genetic variation in the oxidative stress pathway may impact the carcinogenic effect of reactive oxygen species produced by ethanol metabolism. We hypothesized that alcohol interacts with these pathways to affect SCCHN incidence. METHODS: Interview and genotyping data for 64 SNPs were obtained from 2,552 European- and African-American subjects (1,227 cases and 1,325 controls) from the Carolina Head and Neck Cancer Epidemiology Study, a population-based case-control study of SCCHN conducted in North Carolina from 2002 to 2006. We estimated ORs and 95% confidence intervals (CI) for SNPs and haplotypes, adjusting for age, sex, race, and duration of cigarette smoking. P values were adjusted for multiple testing using Bonferroni correction. RESULTS: Two SNPs were associated with SCCHN risk: ADH1B rs1229984 A allele (OR = 0.7; 95% CI, 0.6-0.9) and ALDH2 rs2238151 C allele (OR = 1.2; 95% CI, 1.1-1.4). Three were associated with subsite tumors: ADH1B rs17028834 C allele (larynx, OR = 1.5; 95% CI, 1.1-2.0), SOD2 rs4342445 A allele (oral cavity, OR = 1.3; 95% CI, 1.1-1.6), and SOD2 rs5746134 T allele (hypopharynx, OR = 2.1; 95% CI, 1.2-3.7). Four SNPs in alcohol metabolism genes interacted additively with alcohol consumption: ALDH2 rs2238151, ADH1B rs1159918, ADH7 rs1154460, and CYP2E1 rs2249695. No alcohol interactions were found for oxidative stress SNPs. CONCLUSIONS AND IMPACT: Previously unreported associations of SNPs in ALDH2, CYP2E1, GPX2, SOD1, and SOD2 with SCCHN and subsite tumors provide evidence that alterations in alcohol and oxidative stress pathways influence SCCHN carcinogenesis and warrant further investigation. 21940907 115 135 head and neck cancer Disease D006258 21940907 98 142 squamous cell carcinoma of the head and neck Disease C535575 21940907 144 149 SCCHN Disease C535575 21940907 169 175 cancer Disease D009369 21940907 275 287 carcinogenic Disease D063646 21940907 423 428 SCCHN Disease C535575 21940907 689 694 SCCHN Disease C535575 21940907 995 1000 SCCHN Disease C535575 21940907 1007 1012 ADH1B Gene 125 21940907 1064 1069 ALDH2 Gene 217 21940907 1153 1159 tumors Disease D009369 21940907 1161 1166 ADH1B Gene 125 21940907 1224 1228 SOD2 Gene 6648 21940907 1294 1298 SOD2 Gene 6648 21940907 1425 1444 alcohol consumption Environment 217-C535575 21940907 1425 1444 alcohol consumption Environment 131-C535575 21940907 1425 1444 alcohol consumption Environment 1571-C535575 21940907 1425 1444 alcohol consumption Environment 125-C535575 21940907 1446 1451 ALDH2 Gene 217 21940907 1463 1468 ADH1B Gene 125 21940907 1480 1484 ADH7 Gene 131 21940907 1500 1506 CYP2E1 Gene 1571 21940907 1650 1655 ALDH2 Gene 217 21940907 1657 1663 CYP2E1 Gene 1571 21940907 1665 1669 GPX2 Gene 2877 21940907 1671 1675 SOD1 Gene 6647 21940907 1681 1685 SOD2 Gene 6648 21940907 1691 1696 SCCHN Disease C535575 21940907 1709 1715 tumors Disease D009369 21940907 1753 1760 alcohol Environment 217-C535575 21940907 1753 1760 alcohol Environment 131-C535575 21940907 1753 1760 alcohol Environment 1571-C535575 21940907 1753 1760 alcohol Environment 125-C535575 21940907 1801 1821 SCCHN carcinogenesis Disease 1 10064332|t|MTHFR polymorphism, methyl-replete diets and the risk of colorectal carcinoma and adenoma among U.S. men and women: an example of gene-environment interactions in colorectal tumorigenesis. 10064332|t|Our studies on interactions of a folate-metabolizing gene polymorphism and dietary intake in colorectal tumorigenesis demonstrate the potential importance of studying interactions between genotype and environmental exposure in relation to cancer risk. We observed an inverse association of a polymorphism (667C --> T, ala --> val) in the methylenetetrahydrofolate reductase (MTHFR) gene with colorectal cancer but not with colorectal adenomas. The inverse association of methionine and adverse association of alcohol with colorectal cancer were stronger among val/val individuals. These interactions were not present in studies of colorectal adenomas. Our studies illustrate that studying gene-environment interactions in relation to cancer can be of importance in clarifying cancer etiology as well as pointing to preventive dietary modifications. 10064332 0 5 MTHFR Gene 4524 10064332 57 77 colorectal carcinoma Disease D015179 10064332 82 89 adenoma Disease D000236 10064332 163 187 colorectal tumorigenesis Disease D015179 10064332 93 117 colorectal tumorigenesis Disease D015179 10064332 239 245 cancer Disease D009369 10064332 338 373 methylenetetrahydrofolate reductase Gene 4524 10064332 375 380 MTHFR Gene 4524 10064332 392 409 colorectal cancer Disease D015179 10064332 423 442 colorectal adenomas Disease D015179 10064332 471 481 methionine Environment 4524-D015179 10064332 509 516 alcohol Environment 4524-D015179 10064332 522 539 colorectal cancer Disease D015179 10064332 631 650 colorectal adenomas Disease D015179 10064332 734 740 cancer Disease D009369 10064332 776 782 cancer Disease D009369 19884608|t|Interactive effect of stressful life events and the serotonin transporter 5-HTTLPR genotype on posttraumatic stress disorder diagnosis in 2 independent populations. 19884608|t|CONTEXT: The 5-HTTLPR polymorphism in the promoter region of the serotonin transporter gene (SLC6A4) has been found to moderate several categories of emotional response after stressful life events. Previous studies generally focused on its effect on depressive symptoms; little is known about its moderation of the development of posttraumatic stress disorder (PTSD). OBJECTIVE: To examine the effects of childhood adversity, adult traumatic events, 5-HTTLPR genotypes, and gene x environment interactions on the etiology of PTSD. DESIGN: A cross-sectional study in which participants in several studies investigating the genetics of substance dependence were also screened for lifetime PTSD. The triallelic system of 5-HTTLPR was genotyped. Logistic regression modeling was used in the analyses. SETTING: General community. PARTICIPANTS: Five hundred eighty-two European American and 670 African American individuals who reported experiences of childhood adversity, adult traumatic events, or both. Main Outcome Measure Diagnosis of PTSD, defined by DSM-IV diagnostic criteria and assessed through the Semi-Structured Assessment for Drug Dependence and Alcoholism interview. RESULTS: Childhood adversity and adult traumatic events both predicted PTSD. Although the 5-HTTLPR genotype alone did not predict the onset of PTSD, it interacted with adult traumatic events and childhood adversity to increase the risk for PTSD, especially for those with high rates of both types of trauma exposure (European American: odds ratio [OR], 2.86; 95% confidence interval [CI], 1.50-5.45; P = .002; African American: OR, 1.88; 95% CI, 1.04-3.40; P = .04; pooled: OR, 2.31; 95% CI, 1.50-3.56; P < .001). CONCLUSIONS: Participants who had both childhood adversity and adult traumatic events were more likely to develop lifetime PTSD compared with those who experienced either type of adverse event. The risk was increased in individuals with 1 or 2 copies of the S' (S) allele compared with the L' (L) homozygotes. Our study provides additional direct evidence that PTSD is influenced by the interactive effect of environmental and genetic factors. 19884608 22 43 stressful life events Environment 6532-D013313 19884608 52 73 serotonin transporter Gene 6532 19884608 95 124 posttraumatic stress disorder Disease D013313 19884608 65 86 serotonin transporter Gene 6532 19884608 93 99 SLC6A4 Gene 6532 19884608 250 269 depressive symptoms Disease D003866 19884608 330 359 posttraumatic stress disorder Disease D013313 19884608 361 365 PTSD Disease D013313 19884608 432 441 traumatic Disease D014947 19884608 525 529 PTSD Disease D013313 19884608 634 654 substance dependence Disease D019966 19884608 687 691 PTSD Disease D013313 19884608 973 982 traumatic Disease D014947 19884608 1034 1038 PTSD Disease D013313 19884608 1134 1149 Drug Dependence Disease D019966 19884608 1154 1164 Alcoholism Disease D000437 19884608 1215 1224 traumatic Disease D014947 19884608 1247 1251 PTSD Disease D013313 19884608 1319 1323 PTSD Disease D013313 19884608 1344 1366 adult traumatic events Environment 6532-D013313 19884608 1350 1359 traumatic Disease D014947 19884608 1371 1390 childhood adversity Environment 6532-D013313 19884608 1416 1420 PTSD Disease D013313 19884608 1476 1482 trauma Disease D014947 19884608 1703 1775 Participants who had both childhood adversity and adult traumatic events Environment 6532-D013313 19884608 1759 1768 traumatic Disease D014947 19884608 1813 1817 PTSD Disease D013313 19884608 2051 2055 PTSD Disease D013313 18721261|t|Subtle gene-environment interactions driving paranoia in daily life. 18721261|t|It has been suggested that genes impact on the degree to which minor daily stressors cause variation in the intensity of subtle paranoid experiences. The objective of the present study was to test the hypothesis that catechol-O-methyltransferase (COMT) Val(158)Met and brain-derived neurotrophic factor (BDNF) Val(66)Met in part mediate genetic effects on paranoid reactivity to minor stressors. In a general population sample of 579 young adult female twins, on the one hand, appraisals of (1) event-related stress and (2) social stress and, on the other hand, feelings of paranoia in the flow of daily life were assessed using momentary assessment technology for five consecutive days. Multilevel regression analyses were used to examine moderation of daily life stress-induced paranoia by COMT Val(158)Met and BDNF Val(66)Met genotypes. Catechol-O-methyltransferase Val carriers displayed more feelings of paranoia in response to event stress compared with Met carriers. Brain-derived neurotrophic factor Met carriers showed more social-stress-induced paranoia than individuals with the Val/Val genotype. Thus, paranoia in the flow of daily life may be the result of gene-environment interactions that can be traced to different types of stress being moderated by different types of genetic variation. 18721261 45 53 paranoia Disease D010259 18721261 217 245 catechol-O-methyltransferase Gene 1312 18721261 247 251 COMT Gene 1312 18721261 269 302 brain-derived neurotrophic factor Gene 627 18721261 304 308 BDNF Gene 627 18721261 574 582 paranoia Disease D010259 18721261 780 788 paranoia Disease D010259 18721261 792 796 COMT Gene 1312 18721261 813 817 BDNF Gene 627 18721261 840 868 Catechol-O-methyltransferase Gene 1312 18721261 909 917 paranoia Disease D010259 18721261 933 945 event stress Environment 1312-D010259 18721261 974 1007 Brain-derived neurotrophic factor Gene 627 18721261 1033 1046 social-stress Environment 627-D010259 18721261 1055 1063 paranoia Disease D010259 18721261 1114 1122 paranoia Disease D010259 18721261 1222 1247 different types of stress Environment 627-D010259 18721261 1222 1247 different types of stress Environment 1312-D010259 12594823|t|CYP1A1 T3801 C polymorphism and lung cancer: a pooled analysis of 2451 cases and 3358 controls. 12594823|t|CYP1A1 is involved in the metabolism of benzopyrene, a suspected lung carcinogen; it is therefore conceivable that genetically determined variations in its activity modify individual susceptibility to lung cancer. The role of the CYP1A1 MspI polymorphism in lung cancer has been widely studied but has not been fully clarified. We have included 2,451 cases and 3,358 controls in a pooled analysis of 22 case-control studies on CYP1A1 and lung cancer risk. We found a clear association between the CYP1A1 homozygous MspI restriction fragment length polymorphism (RFLP) and lung cancer risk in Caucasians (age- and gender-adjusted odds ratio = 2.36; 95% confidence interval 1.16-4.81); other associations were weaker or not statistically significant. The association with the homozygous variant was equally strong for squamous cell carcinomas and adenocarcinomas among Caucasians. We analyzed the risk by duration of smoking: for Caucasian subjects with the MspI RFLP combined variants (homozygotes plus heterozygotes), the increase in the risk of lung cancer was steeper than among the individuals with the homozygous reference allele. Our analysis suggests that Caucasians with homozygous variant CYP1A1 polymorphism have a higher risk of lung cancer. The data were more consistent among Caucasians, with a strong association between the homozygous variant in both squamous cell carcinomas and adenocarcinomas, and a stronger association in men than in women. The analyses were more inconsistent and failed to reach statistical significance in Asians. This observation might be due to design specificities or unknown effect modifiers in the Asian studies. 12594823 0 6 CYP1A1 Gene 1543 12594823 7 12 T3801 Gene 1069214 12594823 32 43 lung cancer Disease D008175 12594823 0 6 CYP1A1 Gene 1543 12594823 201 212 lung cancer Disease D008175 12594823 230 236 CYP1A1 Gene 1543 12594823 258 269 lung cancer Disease D008175 12594823 427 433 CYP1A1 Gene 1543 12594823 438 449 lung cancer Disease D008175 12594823 497 503 CYP1A1 Gene 1543 12594823 572 583 lung cancer Disease D008175 12594823 592 602 Caucasians Environment 1543-D008175 12594823 816 840 squamous cell carcinomas Disease D002294 12594823 845 860 adenocarcinomas Disease D000230 12594823 867 877 Caucasians Environment 1543-D002294 12594823 867 877 Caucasians Environment 1543-D000230 12594823 867 877 Caucasians Environment 1543-D008175 12594823 1046 1057 lung cancer Disease D008175 12594823 1162 1172 Caucasians Environment 1543-D008175 12594823 1197 1203 CYP1A1 Gene 1543 12594823 1239 1250 lung cancer Disease D008175 12594823 1288 1298 Caucasians Environment 1543-D002294 12594823 1288 1298 Caucasians Environment 1543-D000230 12594823 1288 1298 Caucasians Environment 1543-D008175 12594823 1365 1389 squamous cell carcinomas Disease D002294 12594823 1394 1409 adenocarcinomas Disease D000230 12594823 1441 1444 men Environment 1543-D008175 19240225|t|Meta- and pooled analysis of GSTP1 polymorphism and lung cancer: a HuGE-GSEC review. 19240225|t|Lung cancer is the most common cancer worldwide. Polymorphisms in genes associated with carcinogen metabolism may modulate risk of disease. Glutathione S-transferase pi (GSTP1) detoxifies polycyclic aromatic hydrocarbons found in cigarette smoke and is the most highly expressed glutathione S-transferase in lung tissue. A polymorphism in the GSTP1 gene, an A-to-G transition in exon 5 (Ile105Val, 313A --> 313G), results in lower activity among individuals who carry the valine allele. The authors present a meta- and a pooled analysis of case-control studies that examined the association between this polymorphism in GSTP1 and lung cancer risk (27 studies, 8,322 cases and 8,844 controls and 15 studies, 4,282 cases and 5,032 controls, respectively). Overall, the meta-analysis found no significant association between lung cancer risk and the GSTP1 exon 5 polymorphism. In the pooled analysis, there was an overall association (odds ratio = 1.11, 95% confidence interval: 1.03, 1.21) between lung cancer and carriage of the GSTP1 Val/Val or Ile/Val genotype compared with those carrying the Ile/Ile genotype. Increased risk varied by histologic type in Asians. There appears to be evidence for interaction between amount of smoking, the GSTP1 exon 5 polymorphism, and risk of lung cancer in whites. 19240225 29 34 GSTP1 Gene 2950 19240225 52 63 lung cancer Disease D008175 19240225 0 11 Lung cancer Disease D008175 19240225 31 37 cancer Disease D009369 19240225 140 165 Glutathione S-transferase Gene 373156 19240225 170 175 GSTP1 Gene 2950 19240225 279 304 glutathione S-transferase Gene 373156 19240225 343 348 GSTP1 Gene 2950 19240225 620 625 GSTP1 Gene 2950 19240225 630 641 lung cancer Disease D008175 19240225 822 833 lung cancer Disease D008175 19240225 847 852 GSTP1 Gene 2950 19240225 996 1007 lung cancer Disease D008175 19240225 1028 1033 GSTP1 Gene 2950 19240225 1157 1163 Asians Environment 2950-D008175 19240225 1218 1235 amount of smoking Environment 2950-D008175 19240225 1241 1246 GSTP1 Gene 2950 19240225 1280 1291 lung cancer Disease D008175 12516098|t|The patched polymorphism Pro1315Leu (C3944T) may modulate the association between use of oral contraceptives and breast cancer risk. 12516098|t|The gene coding for the human homologue of the Drosophila segment polarity gene patched (PTCH1) is mutated in several common human tumors. In mice, haplodeficiency at the Ptch1 locus results in severe histologic defects in mammary ductal structure. We found no mutations within the coding region of PTCH1 in 17 human primary breast carcinomas. However, the biallelic Pro1315Leu (C3944T) polymorphism of PTCH1 was significantly associated with breast cancer in 41 Bavarian patients compared to 85 healthy controls. We investigated whether this variant influences susceptibility for breast cancer in 611 breast cancer patients diagnosed by age 50 years and 1,057 controls matched by age and study region in Germany and in 1,093 breast cancer patients from the United Kingdom. Allele and genotype frequencies were not different between cases and controls. However, multivariate logistic regression analysis revealed an effect modification of oral contraceptive use (OC) on breast cancer risk by Leu-carrier status. Compared to women who have Pro/Pro and never used OC, Pro/Pro OC users had an increased odds ratio for breast cancer of 1.7. The odds ratio was also 1.7 for Leu-carriers who never used OC, but this was attenuated among Leu-carriers who ever used OC by 20%. The gene-environmental interaction was confirmed in case-only analysis of the German and British studies, yielding an interaction odds ratio of 0.7 for premenopausal women (p = 0.06). Longer duration of pill use was associated with a significantly greater risk reduction (p for trend = 0.015). Our novel observation of a differential effect of OC use on breast cancer risk by PTCH1 1315Leu-carrier status suggests the interesting possibility of the Sonic hedgehog/Patched (SHH/PTCH1) signaling pathway being involved in hormone-induced development of breast carcinoma. 12516098 82 108 use of oral contraceptives Environment 5727-D001943 12516098 113 126 breast cancer Disease D001943 12516098 89 94 PTCH1 Gene 5727 12516098 131 137 tumors Disease D009369 12516098 171 176 Ptch1 Gene 5727 12516098 299 304 PTCH1 Gene 5727 12516098 325 342 breast carcinomas Disease D001943 12516098 403 408 PTCH1 Gene 5727 12516098 443 456 breast cancer Disease D001943 12516098 581 594 breast cancer Disease D001943 12516098 602 615 breast cancer Disease D001943 12516098 726 739 breast cancer Disease D001943 12516098 939 966 oral contraceptive use (OC) Environment 5727-D001943 12516098 970 983 breast cancer Disease D001943 12516098 1074 1082 OC users Environment 5727-D001943 12516098 1115 1128 breast cancer Disease D001943 12516098 1613 1619 OC use Environment 5727-D001943 12516098 1623 1636 breast cancer Disease D001943 12516098 1645 1650 PTCH1 Gene 5727 12516098 1742 1745 SHH Gene 6469 12516098 1746 1751 PTCH1 Gene 5727 12516098 1827 1836 carcinoma Disease D002277 15705867|t|Polymorphisms in DNA base excision repair genes ADPRT and XRCC1 and risk of lung cancer. 15705867|t|Adenosine diphosphate ribosyl transferase (ADPRT) and X-ray repair cross-complementing 1 (XRCC1) are two major DNA base excision repair (BER) proteins and act interactively in stimulating and executing BER processes. Polymorphisms of ADPRT Val762Ala and XRCC1 Arg399Gln have been associated with altered protein function and BER activity. This case-control study examined the contribution of these two polymorphisms, alone and in combination, or in interaction with smoking, to the risk of developing lung cancer. We estimated the risk of lung cancer associated with these polymorphisms in 1,000 cases and 1,000 cancer-free controls using logistic regression models. Subjects having the ADPRT Ala/Ala genotype had an odds ratio (OR) of 1.68 [95% confidence interval (95% CI), 1.27-2.23] compared with those having the Val/Val genotype. A greater than multiplicative joint effect between the ADPRT polymorphism and smoking was observed. The ORs (95% CI) of the Ala/Ala genotype for nonsmokers and smokers who smoked < or =16, 16 to 28, or >28 pack-years were 1.13 (0.79-1.62), 1.35 (0.68-2.70), 2.46 (1.35-4.51) or 17.09 (8.15-35.83), respectively (P trend test < 0.001). Gene-gene interaction of ADPRT and XRCC1 polymorphisms increased risk of lung cancer in a supermultiplicative manner (OR for the presence of both ADPRT 762Ala/Ala and XRCC1 399Gln/Gln genotypes, 5.91; 95% CI, 2.09-16.72), although the XRCC1 polymorphism itself was not associated with the risk. In conclusion, the ADPRT Val762Ala polymorphism plays an important role in smoking-related lung cancer and the XRCC1 Arg399Gln polymorphism may serve as a risk modifier. 15705867 48 53 ADPRT Gene 142 15705867 58 63 XRCC1 Gene 7515 15705867 76 87 lung cancer Disease D008175 15705867 0 41 Adenosine diphosphate ribosyl transferase Gene 142 15705867 43 48 ADPRT Gene 142 15705867 54 88 X-ray repair cross-complementing 1 Gene 7515 15705867 90 95 XRCC1 Gene 7515 15705867 234 239 ADPRT Gene 142 15705867 254 259 XRCC1 Gene 7515 15705867 501 512 lung cancer Disease D008175 15705867 539 550 lung cancer Disease D008175 15705867 612 618 cancer Disease D009369 15705867 687 692 ADPRT Gene 142 15705867 891 896 ADPRT Gene 142 15705867 914 921 smoking Environment 142-D008175 15705867 981 991 nonsmokers Environment 142-D008175 15705867 996 1052 smokers who smoked < or =16, 16 to 28, or >28 pack-years Environment 142-D008175 15705867 1196 1201 ADPRT Gene 142 15705867 1206 1211 XRCC1 Gene 7515 15705867 1244 1255 lung cancer Disease D008175 15705867 1317 1322 ADPRT Gene 142 15705867 1338 1343 XRCC1 Gene 7515 15705867 1406 1411 XRCC1 Gene 7515 15705867 1485 1490 ADPRT Gene 142 15705867 1541 1548 smoking Environment 142-D008175 15705867 1557 1568 lung cancer Disease D008175 15705867 1577 1582 XRCC1 Gene 7515 20180012|t|NAT2 polymorphisms combining with smoking associated with breast cancer susceptibility: a meta-analysis. 20180012|t|To derive a more precise estimation of the relationship between the slow or rapid acetylation resulting from N-acetyltransferase 2 (NAT2) polymorphisms and breast cancer risk, a meta-analysis was performed. PubMed, Medline, Embase, and Web of Science were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess strength of association. The pooled ORs were performed for slow versus rapid acetylation genotypes. A total of 26 studies including 9,215 cases and 10,443 controls were included in the meta-analysis. Overall, no significantly elevated breast cancer risk was associated with NAT2 slow genotypes when all studies were pooled into the meta-analysis (OR = 1.026, 95% CI = 0.968-1.087). In the subgroup analysis by ethnicity, increased risks were not found for either Caucasians (OR = 1.001, 95% CI = 0.938-1.068) or Asians (OR = 1.155, 95% CI = 0.886-1.506). When stratified by study design, statistically significantly elevated risk associated with NAT2 slow genotypes was only found among hospital-based studies (OR = 1.178, 95% CI = 1.037-1.339). In the subgroup analysis by menopausal status, no statistically significantly increased risk was found in either premenopausal (OR = 1.053, 95% CI = 0.886-1.252) or postmenopausal women (OR = 0.965, 95% CI = 0.844-1.104). When stratified by cumulative smoking exposure, in the subgroup of smokers with high pack-years, NAT2 slow genotypes were significantly associated with increased breast cancer risk (OR = 1.400, 95% CI = 1.099-1.784). In conclusion, this meta-analysis suggested that there is overall lack of association between NAT2 genotypes and breast cancer risk, however, NAT2 polymorphisms when combining with heavy smoking history may contribute to breast cancer susceptibility. 20180012 0 4 NAT2 Gene 10 20180012 34 41 smoking Environment 10-D001943 20180012 58 71 breast cancer Disease D001943 20180012 109 130 N-acetyltransferase 2 Gene 10 20180012 132 136 NAT2 Gene 10 20180012 156 169 breast cancer Disease D001943 20180012 581 594 breast cancer Disease D001943 20180012 620 624 NAT2 Gene 10 20180012 992 996 NAT2 Gene 10 20180012 1381 1409 smokers with high pack-years Environment 10-D001943 20180012 1411 1415 NAT2 Gene 10 20180012 1476 1489 breast cancer Disease D001943 20180012 1625 1629 NAT2 Gene 10 20180012 1644 1657 breast cancer Disease D001943 20180012 1673 1677 NAT2 Gene 10 20180012 1712 1733 heavy smoking history Environment 10-D001943 20180012 1752 1765 breast cancer Disease D001943 20379847|t|Meta-analysis of two ERCC2 (XPD) polymorphisms, Asp312Asn and Lys751Gln, in breast cancer. 20379847|t|The excision repair cross-complementing group 2 gene (ERCC2) plays a key role in DNA repair. Several polymorphisms in the ERCC2 gene have been described, including the commonly occurring Lys751Gln and Asp312Asn polymorphisms. Studies investigating the association of these polymorphisms with breast cancer risk produced controversial results. To evaluate these associations presented in diverse populations, we have conducted a meta-analysis based on 40 studies from 33 publications in PubMed which included analyses of Lys751Gln (14,545 cases, 15,352 controls) and Asp312Asn polymorphisms (16,254 cases, 14,006 controls). Overall findings of both polymorphisms have implicated null effects (OR = 1.01-1.03) when the analyses were limited to the statistically powerful (>/=80%) studies. Although modestly increased statistically significant breast cancer risk was detected in the underpowered studies (55 years old (OR = 1.57, 95% CI = 1.10-2.23), males (OR = 1.88, 95% CI = 1.22-2.89), current (OR = 2.04, 95% CI = 1.26-3.29) and heavy smokers (OR = 1.73, 95% CI = 1.10-2.70) and current drinkers (OR = 3.17, 95% CI = 1.78-5.64).Furthermore, significant gene-dietary interactions were found between TS3'UTR and alcohol consumption and between TSER and vitamin B(12) intake. In conclusion, the polymorphisms of TYMS are likely to contribute to the risk of lung cancer in non-Hispanic whites and interact with dietary factors in lung cancer development. 15579479 25 45 thymidylate synthase Gene 7298 15579479 72 83 lung cancer Disease D008175 15579479 56 67 lung cancer Disease D008175 15579479 149 160 lung cancer Disease D008175 15579479 167 187 Thymidylate synthase Gene 7298 15579479 189 193 TYMS Gene 7298 15579479 326 330 TYMS Gene 7298 15579479 380 391 lung cancer Disease D008175 15579479 397 401 TYMS Gene 7298 15579479 468 472 TYMS Gene 7298 15579479 701 712 lung cancer Disease D008175 15579479 731 737 cancer Disease D009369 15579479 915 926 lung cancer Disease D008175 15579479 1080 1091 lung cancer Disease D008175 15579479 1283 1296 >55 years old Environment 7298-D008175 15579479 1330 1335 males Environment 7298-D008175 15579479 1413 1426 heavy smokers Environment 7298-D008175 15579479 1463 1479 current drinkers Environment 7298-D008175 15579479 1542 1549 dietary Environment 7298-D008175 15579479 1594 1613 alcohol consumption Environment 7298-D008175 15579479 1635 1655 vitamin B(12) intake Environment 7298-D008175 15579479 1693 1697 TYMS Gene 7298 15579479 1738 1749 lung cancer Disease D008175 15579479 1791 1806 dietary factors Environment 7298-D008175 15579479 1810 1821 lung cancer Disease D008175 21719879|t|Childhood abuse, the BDNF-Val66Met polymorphism and adult psychotic-like experiences. 21719879|t|BACKGROUND: The well-established relationship between childhood adversity and psychosis is likely to involve other factors such as genetic variants that can help us to understand why not everyone exposed to adverse events develops psychotic symptoms later in life. AIMS: We investigated the influence of childhood abuse and neglect on positive and negative psychotic-like experiences in adulthood and the potential moderating effect of the BDNF-Val66Met polymorphism. METHOD: Psychotic-like experiences and childhood adversity were assessed in 533 individuals from the general population. RESULTS: Childhood abuse showed a strong independent effect on the positive dimension of psychotic-like experiences (beta = 0.16, s.e. = 0.05, P = 0.002). Furthermore, this association was moderated by the BDNF-Val66Met polymorphism (beta = 0.27, s.e. = 0.10, P = 0.004). CONCLUSIONS: Individuals exposed to childhood abuse are more likely to report positive psychotic-like experiences. Met carriers reported more positive psychotic-like experiences when exposed to childhood abuse than did individuals carrying the Val/Val genotype. Therefore, the observed gene-environment interaction effect may be partially responsible for individual variation in response to childhood abuse. 21719879 21 25 BDNF Gene 627 21719879 58 67 psychotic Disease D011618 21719879 78 87 psychosis Disease D011605 21719879 231 249 psychotic symptoms Disease D011605 21719879 357 366 psychotic Disease D011618 21719879 440 444 BDNF Gene 627 21719879 476 485 Psychotic Disease D011618 21719879 598 613 Childhood abuse Environment 627-D011618 21719879 678 687 psychotic Disease D011618 21719879 795 799 BDNF Gene 627 21719879 897 912 childhood abuse Environment 627-D011618 21719879 948 957 psychotic Disease D011618 21719879 1012 1021 psychotic Disease D011618 21719879 1252 1267 childhood abuse Environment 627-D011618 19205873|t|A polymorphism in Werner syndrome gene is associated with breast cancer susceptibility in Chinese women. 19205873|t|RecQ helicases play a central role in maintaining genome stability and may interact with some important cancer-related proteins such as BRCA1. Mutations of the human RecQ helicase genes WRN and BLM lead to rare autosomal recessive disorders, Werner and Bloom syndromes, which are associated with premature aging and cancer predisposition, including breast cancer. In this case-control study of 1,004 breast cancer cases and 1,008 controls, we tested the hypothesis that non-conservative amino acid exchanges in WRN (leu1074Phe), BLM (Met298Thr) and BRCA1 (Pro871Leu) are independently or jointly associated with the risk of breast cancer in Chinese women. We found that the variant genotype of WRN Leu1074Phe was associated with a 1.36-fold significantly increased risk of breast cancer (OR = 1.36, 95% CI = 1.06-1.74). Moreover, a significant gene-environment interaction was evident between WRN leu1074Phe and age at menarche (P (int) = 0.02). Subjects carrying Phe/Phe genotype and with earlier age at menarche had 3.58-fold increased risk of breast cancer (OR = 3.58, 95% CI = 2.54-5.05). However, we did not find the significant main effect of polymorphisms in BLM and BRCA1 and also no locus-locus interactions were identified between WRN, BLM and BRCA1. These findings indicate that WRN leu1074Phe variant may contribute to the susceptibility of breast cancer in Chinese women. 19205873 18 33 Werner syndrome Disease D014898 19205873 58 71 breast cancer Disease D001943 19205873 50 66 genome stability Disease D042822 19205873 104 110 cancer Disease D009369 19205873 136 141 BRCA1 Gene 672 19205873 186 189 WRN Gene 7486 19205873 221 240 recessive disorders Disease D030342 19205873 296 311 premature aging Disease D019588 19205873 316 322 cancer Disease D009369 19205873 349 362 breast cancer Disease D001943 19205873 400 413 breast cancer Disease D001943 19205873 511 514 WRN Gene 7486 19205873 549 554 BRCA1 Gene 672 19205873 624 637 breast cancer Disease D001943 19205873 694 697 WRN Gene 7486 19205873 773 786 breast cancer Disease D001943 19205873 893 896 WRN Gene 7486 19205873 912 927 age at menarche Environment 7486-D001943 19205873 990 1013 earlier age at menarche Environment 7486-D001943 19205873 1047 1060 breast cancer Disease D001943 19205873 1175 1180 BRCA1 Gene 672 19205873 1242 1245 WRN Gene 7486 19205873 1255 1260 BRCA1 Gene 672 19205873 1291 1294 WRN Gene 7486 19205873 1354 1367 breast cancer Disease D001943 18340529|t|A prospective study of genetic polymorphism in MPO, antioxidant status, and breast cancer risk. 18340529|t|Oxidative stress may be involved in breast carcinogenesis. Myeloperoxidase (MPO) is an endogenous oxidant enzyme that generates reactive oxygen species (ROS). A single nucleotide polymorphism (SNP) G-463A in the promoter region has been associated with a decrease in risk of breast cancer. We assessed the association between this polymorphism and breast cancer risk in a nested case-control study within the Nurses' Health Study (1,269 incident breast cancer cases and 1,761 matched controls). We further investigated potential gene-gene and gene-environment interactions. There were no significant associations between MPO or COMT genotypes and risk of breast cancer. However, the combination of a priori hypothesized low-risk genotypes in MPO and COMT genes was associated with a marginally significant decrease in breast cancer risk (OR, 0.28; 95% CI, 0.08-1.00). Dietary intake and plasma antioxidant levels may modify the association between the MPO polymorphism and breast cancer risk. Although the test for departure from multiplicative interaction was not significant, inverse associations with MPO genotype were more pronounced among women who consumed higher amounts of total fruits and vegetables (OR, 0.58; 95% CI, 0.30-1.12); this association was not found among the low-consumption group (OR, 1.11; 95% CI, 0.63-1.96). The relative risk associated with the MPO homozygous variant genotype was 0.44 (95% CI, 0.18-1.09) for women who had the highest level of plasma carotenoids. Results from this study suggest that exogenous and endogenous modulators of oxidative stress may modify the association between the MPO polymorphism and breast cancer risk. Further research is needed to confirm these possible associations. 18340529 47 50 MPO Gene 4353 18340529 76 89 breast cancer Disease D001943 18340529 43 57 carcinogenesis Disease D063646 18340529 59 74 Myeloperoxidase Gene 4353 18340529 76 79 MPO Gene 4353 18340529 275 288 breast cancer Disease D001943 18340529 348 361 breast cancer Disease D001943 18340529 446 459 breast cancer Disease D001943 18340529 621 624 MPO Gene 4353 18340529 628 632 COMT Gene 1312 18340529 655 668 breast cancer Disease D001943 18340529 742 745 MPO Gene 4353 18340529 750 754 COMT Gene 1312 18340529 818 831 breast cancer Disease D001943 18340529 868 882 Dietary intake Environment 4353-D001943 18340529 887 912 plasma antioxidant levels Environment 4353-D001943 18340529 952 955 MPO Gene 4353 18340529 973 986 breast cancer Disease D001943 18340529 1104 1107 MPO Gene 4353 18340529 1163 1208 higher amounts of total fruits and vegetables Environment 4353-D001943 18340529 1372 1375 MPO Gene 4353 18340529 1451 1490 the highest level of plasma carotenoids Environment 4353-D001943 18340529 1529 1584 exogenous and endogenous modulators of oxidative stress Environment 4353-D001943 18340529 1624 1627 MPO Gene 4353 18340529 1645 1658 breast cancer Disease D001943 18383516|t|The modifying effect of C-reactive protein gene polymorphisms on the association between central obesity and endometrial cancer risk. 18383516|t|BACKGROUND: Obesity is a major risk factor for endometrial cancer. Obesity, particularly central obesity, is considered as a systemic inflammatory condition and is related strongly to insulin resistance. C-reactive protein (CRP) is the most recognized biologic marker of chronic systematic inflammation, and it is conceivable that the CRP gene may work together with obesity in the development of endometrial cancer. METHODS: On the basis of a population-based case-control study in a Chinese population, the authors obtained obesity measurements and data on 6 CRP single-nucleotide polymorphisms (SNPs) from 1046 patients with newly diagnosed endometrial cancer (cases) and from 1035 age frequency-matched controls. The association of the CRP SNPs with endometrial cancer risk and their modification on the association between obesity and endometrial cancer risk were evaluated. RESULTS: Although CRP SNPs alone were not associated with endometrial cancer, the associations of endometrial cancer with central obesity, measured as the waist-to-hip ratio (WHR) and the waist circumference, seemed to be stronger in women who were homozygous for the major allele of reference SNP (rs)1130864 (cytidine [C]/C) than in women who had the C/thymidine (T) and T/T genotypes (interaction test: P = .013 for WHR; P = .083 for waist circumference). When the women were stratified further by menopausal status, the observed interactions persisted mainly in premenopausal women (interaction test: P < .001 for WHR; P = .002 for waist circumference). CONCLUSIONS: The current results suggested that, in the Chinese population that was studied, obesity-related insulin resistance and proinflammatory effects may play an important role in endometrial cancer risk, and these effects were modified significantly by the CRP SNP rs1130864. 18383516 24 42 C-reactive protein Gene 1401 18383516 89 104 central obesity Disease D056128 18383516 89 104 central obesity Environment 1401-D016889 18383516 109 127 endometrial cancer Disease D016889 18383516 12 19 Obesity Disease D009765 18383516 47 65 endometrial cancer Disease D016889 18383516 67 74 Obesity Disease D009765 18383516 89 104 central obesity Disease D056128 18383516 204 222 C-reactive protein Gene 1401 18383516 224 227 CRP Gene 1401 18383516 290 302 inflammation Disease D007249 18383516 335 338 CRP Gene 1401 18383516 367 374 obesity Disease D009765 18383516 397 415 endometrial cancer Disease D016889 18383516 526 533 obesity Disease D009765 18383516 561 564 CRP Gene 1401 18383516 644 662 endometrial cancer Disease D016889 18383516 740 743 CRP Gene 1401 18383516 754 772 endometrial cancer Disease D016889 18383516 828 835 obesity Disease D009765 18383516 840 858 endometrial cancer Disease D016889 18383516 898 901 CRP Gene 1401 18383516 938 956 endometrial cancer Disease D016889 18383516 978 996 endometrial cancer Disease D016889 18383516 1002 1017 central obesity Disease D056128 18383516 1002 1017 central obesity Environment 1401-D016889 18383516 1446 1465 premenopausal women Environment 1401-D016889 18383516 1631 1638 obesity Disease D009765 18383516 1631 1665 obesity-related insulin resistance Environment 1401-D016889 18383516 1670 1693 proinflammatory effects Environment 1401-D016889 18383516 1724 1742 endometrial cancer Disease D016889 18383516 1802 1805 CRP Gene 1401 18808401|t|COMT ValMet moderation of cannabis-induced psychosis: a momentary assessment study of 'switching on' hallucinations in the flow of daily life. 18808401|t|OBJECTIVE: A functional polymorphism in the catechol-o-methyltransferase gene (COMT Val(158)Met) may moderate the psychosis-inducing effects of cannabis. In order to extend this finding to dynamic effects in the flow of daily life, a momentary assessment study of psychotic symptoms in response to cannabis use was conducted. METHOD: The experience sampling technique was used to collect data on cannabis use and occurrence of symptoms in daily life in patients with a psychotic disorder (n = 31) and healthy controls (n = 25). RESULTS: Carriers of the COMT Val(158)Met Val allele, but not subjects with the Met/Met genotype, showed an increase in hallucinations after cannabis exposure, conditional on prior evidence of psychometric psychosis liability. CONCLUSION: The findings confirm that in people with psychometric evidence of psychosis liability, COMT Val(158)Met genotype moderates the association between cannabis and psychotic phenomena in the flow of daily life. 18808401 0 4 COMT Gene 1312 18808401 26 34 cannabis Environment 1312-D011618 18808401 26 34 cannabis Environment 1312-D006212 18808401 43 52 psychosis Disease D011605 18808401 101 115 hallucinations Disease D006212 18808401 44 72 catechol-o-methyltransferase Gene 1312 18808401 79 83 COMT Gene 1312 18808401 114 123 psychosis Disease D011605 18808401 144 152 cannabis Environment 1312-D011618 18808401 264 282 psychotic symptoms Disease D011605 18808401 469 487 psychotic disorder Disease D011618 18808401 553 557 COMT Gene 1312 18808401 648 662 hallucinations Disease D006212 18808401 669 686 cannabis exposure Environment 1312-D011618 18808401 669 686 cannabis exposure Environment 1312-D006212 18808401 734 743 psychosis Disease D011605 18808401 833 842 psychosis Disease D011605 18808401 854 858 COMT Gene 1312 18808401 932 941 psychotic Disease D011618 20935061|t|A novel functional DEC1 promoter polymorphism -249T>C reduces risk of squamous cell carcinoma of the head and neck. 20935061|t|Human DEC1 (deleted in esophageal cancer 1) gene is located on chromosome 9q, a region frequently deleted in various types of human cancers, including squamous cell carcinoma of the head and neck (SCCHN). However, only one epidemiological study has evaluated the association between DEC1 polymorphisms and cancer risk. In this hospital-based case-control study, four potentially functional single-nucleotide polymorphisms -1628 G>A (rs1591420), -606 T>C [rs4978620, in complete linkage disequilibrium with -249T>C (rs2012775) and -122 G>A(rs2012566)], c.179 C>T p.Ala60Val (rs2269700) and 3' untranslated region-rs3750505 as well as the TP53 tumor suppressor gene codon 72 (Arg72Pro, rs1042522) polymorphism were genotyped in 1111 non-Hispanic Whites SCCHN patients and 1130 age-and sex-matched cancer-free controls. After adjustment for age, sex and smoking and drinking status, the variant -606CC (i.e. -249CC) homozygotes had a significantly reduced SCCHN risk (adjusted odds ratio = 0.71, 95% confidence interval = 0.52-0.99) compared with the -606TT homozygotes. Stratification analyses showed that a reduced risk associated with the -606CC genotype was more pronounced in subgroups of non-smokers, non-drinkers, younger subjects (defined as C (rs2012775) polymorphism is functional, modulating susceptibility to SCCHN among non-Hispanic Whites. 20935061 19 23 DEC1 Gene 50514 20935061 70 114 squamous cell carcinoma of the head and neck Disease C535575 20935061 6 10 DEC1 Gene 50514 20935061 12 42 deleted in esophageal cancer 1 Gene 50514 20935061 23 40 esophageal cancer Disease D004938 20935061 132 139 cancers Disease D009369 20935061 151 195 squamous cell carcinoma of the head and neck Disease C535575 20935061 197 202 SCCHN Disease C535575 20935061 283 287 DEC1 Gene 50514 20935061 306 312 cancer Disease D009369 20935061 637 641 TP53 Gene 7157 20935061 642 647 tumor Disease D009369 20935061 751 756 SCCHN Disease C535575 20935061 795 801 cancer Disease D009369 20935061 953 958 SCCHN Disease C535575 20935061 1191 1202 non-smokers Environment 50514-C535575 20935061 1204 1216 non-drinkers Environment 50514-C535575 20935061 1218 1234 younger subjects Environment 50514-C535575 20935061 1247 1258 H, 5'-UTR C > T, and K337K G > A) were genotyped by the primer extension assay. The CASP8 D302H, which was not polymorphic in 48 samples, was excluded in further genotyping. Odds ratios and 95% confidential intervals (95% CIs) were estimated by unconditional logistic regression model adjusted for age at enrollment, education, age at first full-term pregnancy, cigarette smoking, and family history of breast cancer. RESULTS: The 5'-UTR T allele containing genotypes (CT/TT) were associated with an increased risk of breast cancer, compared with those with the CC genotype (OR = 1.13, 95% CI = 0.95-1.34; and OR = 1.48, 95% CI = 1.04-2.10, respectively; P-trend = 0.02). When stratified by the estrogen and progesterone receptor status, the association between the 5'-UTR T allele and breast cancer risk was prominent in ER(+) and PR(+) cases among pre-menopausal women (OR = 1.31, 95% CI = 1.00-1.72 and OR = 1.40, 95% CI = 1.06-1.85, respectively), whereas the association was found prominent in ER(-) or PR(-) cases (OR = 1.32, 95% CI = 0.93-1.87 and OR = 1.42, 95% CI = 1.04-1.94, respectively) among post-menopausal women. CONCLUSION: Our results thus suggest that the CASP8 5'-UTR C > T are associated with breast cancer risks and the effect may be modified by estrogen and progesterone receptor status. 17940865 0 5 CASP8 Gene 841 17940865 34 55 progesterone receptor Gene 5241 17940865 68 81 breast cancer Disease D001943 17940865 71 76 CASP8 Gene 841 17940865 118 131 breast cancer Disease D001943 17940865 182 195 breast cancer Disease D001943 17940865 540 545 CASP8 Gene 841 17940865 859 872 breast cancer Disease D001943 17940865 974 987 breast cancer Disease D001943 17940865 1164 1185 progesterone receptor Gene 5241 17940865 1242 1255 breast cancer Disease D001943 17940865 1278 1283 ER(+) Environment 841-D001943 17940865 1288 1293 PR(+) Environment 841-D001943 17940865 1455 1460 ER(-) Environment 841-D001943 17940865 1464 1469 PR(-) Environment 841-D001943 17940865 1631 1636 CASP8 Gene 841 17940865 1670 1683 breast cancer Disease D001943 17940865 1724 1765 estrogen and progesterone receptor status Environment 841-D001943 17940865 1737 1758 progesterone receptor Gene 5241 16614128|t|OGG1 polymorphisms and breast cancer risk. 16614128|t|The role of oxidative stress in breast cancer risk is still unclear. OGG1 encodes an 8-oxoguanine DNA glycosylase/AP lyase that catalyzes the removal of 8-oxodeoxyguanosine from DNA. 8-Oxodeoxyguanosine, the most abundant lesion generated by oxidative stress, is highly mutagenic. Environmental sources of oxidative stress, such as alcohol consumption, cigarette smoking, high body mass index (BMI), and low fruits and vegetables intake, may modify the association of genetic polymorphisms with breast cancer risk. We investigated the association between three genetic polymorphisms in OGG1 (Ser(326)Cys, 7143A/G, and 11657A/G) and breast cancer risk among 1,058 cases and 1,102 controls participating in the Long Island Breast Cancer Study Project. No associations were observed between individual OGG1 polymorphisms, haplotypes, or diplotypes and breast cancer. The association between having at least one variant allele and breast cancer risk was stronger among moderate alcohol drinkers for Ser(326)Cys [odds ratio (OR), 1.82; 95% confidence interval (95% CI), 1.06-3.10] relative to nondrinkers with the wild-type genotype and among those with higher BMI for 7143A/G (OR, 1.47; 95% CI, 1.10-1.96) and for 11657A/G (OR, 1.41; 95% CI, 1.05-1.88), relative to women with BMI < 25 kg/m(2) and the wild-type genotype. However, the patterns were not seen for all three single nucleotide polymorphisms (SNP) nor were there any clear allele dose associations; only one interaction was statistically significant, assuming a multiplicative model (11657A/G, P(interaction) = 0.04). In summary, although we found some differences between the three OGG1 SNPs and breast cancer risk among moderate alcohol drinkers and women with higher BMI, replication of these results is needed to rule out spurious findings. In addition, data on functionality of these polymorphisms are crucial to understand if these modest differences are important. 16614128 0 4 OGG1 Gene 4968 16614128 23 36 breast cancer Disease D001943 16614128 32 45 breast cancer Disease D001943 16614128 69 73 OGG1 Gene 4968 16614128 85 113 8-oxoguanine DNA glycosylase Gene 4968 16614128 114 122 AP lyase Gene 4968 16614128 495 508 breast cancer Disease D001943 16614128 586 590 OGG1 Gene 4968 16614128 632 645 breast cancer Disease D001943 16614128 799 803 OGG1 Gene 4968 16614128 849 862 breast cancer Disease D001943 16614128 927 940 breast cancer Disease D001943 16614128 965 990 moderate alcohol drinkers Environment 4968-D001943 16614128 1149 1159 higher BMI Environment 4968-D001943 16614128 1641 1645 OGG1 Gene 4968 16614128 1655 1668 breast cancer Disease D001943 16614128 1680 1705 moderate alcohol drinkers Environment 4968-D001943 16614128 1721 1731 higher BMI Environment 4968-D001943 19357867|t|P53 polymorphism and lung cancer susceptibility: a pooled analysis of 32 case-control studies. 19357867|t|To explore the real association between p53 codon 72 polymorphism and lung cancer risk, a pooled analysis of 32 case-control studies involving 19,255 subjects was conducted. When all 32 studies were pooled into the analysis, significantly elevated lung cancer risks were associated with variant genotypes in all genetic models (for Pro/Arg vs. Arg/Arg: OR 1.21, 95% CI 1.01-1.23; for Pro/Pro vs. Arg/Arg: OR 1.20, 95% CI 1.03-1.39; for Pro/Pro + Pro/Arg vs. Arg/Arg: OR 1.14, 95% CI 1.03-1.25; for Pro/Pro vs. Arg/Arg + Pro/Arg: OR 1.06, 95% CI 1.01-1.12). In the subgroup analysis by ethnicity, histological type, or smoking status, significantly increased risks were found in subgroups such as Asians, Caucasians, lung adenocarcinoma patients, or smokers, respectively. In conclusion, our results suggest that the Pro allele at p53 codon 72 is emerging as a low-penetrance susceptibility allele for lung cancer development. 19357867 0 3 P53 Gene 7157 19357867 21 32 lung cancer Disease D008175 19357867 40 43 p53 Gene 7157 19357867 70 81 lung cancer Disease D008175 19357867 248 259 lung cancer Disease D008175 19357867 353 360 OR 1.21 Gene 128371 19357867 467 474 OR 1.14 Gene 128367 19357867 696 702 Asians Environment 7157-D008175 19357867 704 714 Caucasians Environment 7157-D008175 19357867 716 735 lung adenocarcinoma Disease C538231 19357867 716 744 lung adenocarcinoma patients Environment 7157-D008175 19357867 749 756 smokers Environment 7157-D008175 19357867 830 833 p53 Gene 7157 19357867 901 912 lung cancer Disease D008175 19549808|t|Oral contraceptive use and BRCA penetrance: a case-only study. 19549808|t|BACKGROUND: Women with deleterious mutations in BRCA genes are at increased risk of breast cancer. However, the penetrance of the genetic trait may be regulated through environmental factors. This multinational case-only study tested the interaction between oral contraceptive use and genetic susceptibility in the occurrence of breast cancer. METHODS: We recruited 3,123 patients diagnosed with breast cancer before the age of 45 years. Participants were classified according to their probability of carrying a BRCA mutation on the basis of their family history of breast and ovarian cancer. According to a case-only approach, the frequency of relevant exposures among breast cancer cases with high probability of BRCA mutation ("genetic cases") was compared with the frequency of the same exposures among breast cancer cases with a low probability of BRCA mutation ("sporadic cases"). The interaction odds ratios (OR) and 95% confidence intervals (CI) for oral contraceptive use were estimated by unconditional logistic regression, after controlling for potentially confounding variables. RESULTS: The analysis was carried out comparing 382 "genetic" and 1,333 "sporadic" cases. We found a borderline significant interaction between genetic breast cancer and oral contraceptive use for ever users compared with never users (OR, 1.3; 95% CI, 1.0-1.7). The greatest interaction OR was found for women who started using pill at 18 to 20 years (OR, 1.6; 95% CI, 1.1-2.3). CONCLUSION: These results suggest that BRCA mutation carriers, as well as women with a significant family history of breast and ovarian cancer are more vulnerable to exogenous hormones in oral contraceptives. 19549808 27 31 BRCA Gene 672 19549808 48 52 BRCA Gene 672 19549808 84 97 breast cancer Disease D001943 19549808 285 292 genetic Disease 1 19549808 329 342 breast cancer Disease D001943 19549808 396 409 breast cancer Disease D001943 19549808 512 516 BRCA Gene 672 19549808 566 591 breast and ovarian cancer Disease D061325 19549808 670 683 breast cancer Disease D001943 19549808 715 719 BRCA Gene 672 19549808 807 820 breast cancer Disease D001943 19549808 853 857 BRCA Gene 672 19549808 1243 1256 breast cancer Disease D001943 19549808 1261 1298 oral contraceptive use for ever users Environment 672-D001943 19549808 1509 1513 BRCA Gene 672 19549808 1587 1612 breast and ovarian cancer Disease D061325 19549808 1636 1677 exogenous hormones in oral contraceptives Environment 672-D001943 19479063|t|Phase I metabolic genes and risk of lung cancer: multiple polymorphisms and mRNA expression. 19479063|t|Polymorphisms in genes coding for enzymes that activate tobacco lung carcinogens may generate inter-individual differences in lung cancer risk. Previous studies had limited sample sizes, poor exposure characterization, and a few single nucleotide polymorphisms (SNPs) tested in candidate genes. We analyzed 25 SNPs (some previously untested) in 2101 primary lung cancer cases and 2120 population controls from the Environment And Genetics in Lung cancer Etiology (EAGLE) study from six phase I metabolic genes, including cytochrome P450s, microsomal epoxide hydrolase, and myeloperoxidase. We evaluated the main genotype effects and genotype-smoking interactions in lung cancer risk overall and in the major histology subtypes. We tested the combined effect of multiple SNPs on lung cancer risk and on gene expression. Findings were prioritized based on significance thresholds and consistency across different analyses, and accounted for multiple testing and prior knowledge. Two haplotypes in EPHX1 were significantly associated with lung cancer risk in the overall population. In addition, CYP1B1 and CYP2A6 polymorphisms were inversely associated with adenocarcinoma and squamous cell carcinoma risk, respectively. Moreover, the association between CYP1A1 rs2606345 genotype and lung cancer was significantly modified by intensity of cigarette smoking, suggesting an underlying dose-response mechanism. Finally, increasing number of variants at CYP1A1/A2 genes revealed significant protection in never smokers and risk in ever smokers. Results were supported by differential gene expression in non-tumor lung tissue samples with down-regulation of CYP1A1 in never smokers and up-regulation in smokers from CYP1A1/A2 SNPs. The significant haplotype associations emphasize that the effect of multiple SNPs may be important despite null single SNP-associations, and warrants consideration in genome-wide association studies (GWAS). Our findings emphasize the necessity of post-GWAS fine mapping and SNP functional assessment to further elucidate cancer risk associations. 19479063 36 47 lung cancer Disease D008175 19479063 126 137 lung cancer Disease D008175 19479063 358 369 lung cancer Disease D008175 19479063 442 453 Lung cancer Disease D008175 19479063 573 588 myeloperoxidase Gene 4353 19479063 666 677 lung cancer Disease D008175 19479063 778 789 lung cancer Disease D008175 19479063 995 1000 EPHX1 Gene 2052 19479063 1036 1047 lung cancer Disease D008175 19479063 1093 1099 CYP1B1 Gene 1545 19479063 1104 1110 CYP2A6 Gene 1548 19479063 1156 1170 adenocarcinoma Disease D000230 19479063 1175 1198 squamous cell carcinoma Disease D002294 19479063 1253 1259 CYP1A1 Gene 1543 19479063 1283 1294 lung cancer Disease D008175 19479063 1325 1355 intensity of cigarette smoking Environment 1543-D008175 19479063 1449 1455 CYP1A1 Gene 1543 19479063 1500 1513 never smokers Environment 1543-D008175 19479063 1526 1538 ever smokers Environment 1543-D008175 19479063 1602 1607 tumor Disease D009369 19479063 1652 1658 CYP1A1 Gene 1543 19479063 1662 1675 never smokers Environment 1543-D008175 19479063 1697 1704 smokers Environment 1543-D008175 19479063 1710 1716 CYP1A1 Gene 1543 19479063 2047 2053 cancer Disease D009369 21041608|t|Family-based analysis of genetic variation underlying psychosis-inducing effects of cannabis: sibling analysis and proband follow-up. 21041608|t|CONTEXT: Individual differences exist in sensitivity to the psychotomimetic effect of cannabis; the molecular genetic basis underlying differential sensitivity remains elusive. OBJECTIVE: To investigate whether selected schizophrenia candidate single-nucleotide polymorphisms (SNPs) moderate effects of cannabis use. DESIGN: Interactions between recent cannabis use, determined by urinalysis results, and 152 SNPs in 42 candidate genes were examined in 740 unaffected siblings of 801 patients with psychosis to examine genetic moderation of the association between Structured Interview for Schizotypy-Revised positive schizotypy and recent cannabis use (at-risk paradigm). The SNPs showing Bonferroni-adjusted association in the at-risk paradigm were used in a case-only analysis in the 801 patients, as well as in a case-sibling and case-control analysis (using 419 controls) focusing on genetic moderation of developmental effects of cannabis on later psychotic disorder. SETTING: The Netherlands and Flanders, Belgium. PARTICIPANTS: Eight hundred one patients with psychosis and their 740 unaffected siblings. MAIN OUTCOME MEASURE: Significant interaction between any of the selected SNPs and cannabis in the at-risk paradigm, followed by selective case-only, case-sibling, and case-control analyses. RESULTS: In the unaffected siblings, 16 SNPs in 12 genes showed significant interaction at P < .05, 3 of which survived correction for multiple testing (P < .0003), situated in AKT1 (rs2494732 and rs1130233) and LRRTM1 (rs673871). Follow-up analysis supported AKT1 rs2494732 x cannabis interaction in the case-only (beta = 0.20; P = .007), case-sibling (interaction P = .040), and case-control (interaction P = .057) analyses, with individuals with C/C genotypes having an approximately 2-fold odds of being diagnosed with a psychotic disorder when having used cannabis. In the unaffected siblings, the AKT1 x cannabis interaction explained 2.2% additional variance in schizotypy in the whole sample and 19.0% additional variance in the exposed siblings with recent cannabis use. CONCLUSIONS: Genetic variation in AKT1 may mediate both short-term as well as longer-term effects on psychosis expression associated with use of cannabis, possibly through a mechanism of cannabinoid-regulated AKT1/GSK-3 signaling downstream of the dopamine D(2) receptor. 21041608 54 63 psychosis Disease D011605 21041608 220 233 schizophrenia Disease D012559 21041608 498 507 psychosis Disease D011605 21041608 954 972 psychotic disorder Disease D011618 21041608 1068 1077 psychosis Disease D011605 21041608 1481 1485 AKT1 Gene 207 21041608 1516 1522 LRRTM1 Gene 347730 21041608 1564 1568 AKT1 Gene 207 21041608 1581 1589 cannabis Environment 207-D011618 21041608 1581 1589 cannabis Environment 207-D012559 21041608 1829 1847 psychotic disorder Disease D011618 21041608 1865 1873 cannabis Environment 207-D011618 21041608 1865 1873 cannabis Environment 207-D012559 21041608 1907 1911 AKT1 Gene 207 21041608 1914 1922 cannabis Environment 207-D011618 21041608 1914 1922 cannabis Environment 207-D012559 21041608 2037 2082 the exposed siblings with recent cannabis use Environment 207-D011618 21041608 2037 2082 the exposed siblings with recent cannabis use Environment 207-D012559 21041608 2118 2122 AKT1 Gene 207 21041608 2185 2194 psychosis Disease D011605 21041608 2222 2237 use of cannabis Environment 207-D011618 21041608 2222 2237 use of cannabis Environment 207-D012559 21041608 2293 2297 AKT1 Gene 207 21041608 2332 2354 dopamine D(2) receptor Gene 1813 22385256|t|A genetic variant in 3'-untranslated region of cyclooxygenases-2 gene is associated with risk of gastric cancer in a Chinese population. 22385256|t|Cyclooxygenase-2 (COX-2) involves in multiple processes in carcinogenesis, including inflammation, apoptosis inhibition, immune response suppression, tumor cell invasion, and angiogenesis. COX-2 is overexpressed in various cancers, including gastric cancer. COX-2 is encoded by prostaglandin endoperoxide synthase 2 (PTGS2) gene. We hypothesized that potentially functional polymorphisms in PTGS2 may contribute to gastric cancer risk. To assess this hypothesis, we conducted a case-control study with 1681 gastric cancer cases and 1916 control subjects in a Chinese population to evaluate the association between a polymorphism in 3'-untranslated region of PTGS2, rs5275, and the risk of gastric cancer. Logistic regression analysis revealed that variant allele (C) of rs5275 was significantly associated with an increased risk of gastric cancer (per allele odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.01-1.29, p = 0.030). This association was more prominent in females (per allele OR = 1.42, 95% CI = 1.11-1.81, p = 0.005) and nonsmokers (per allele OR = 1.35, 95% CI = 1.14-1.59, p = 0.001). Interestingly, we detected a negative interaction between rs5275 and smoking on the gastric cancer risk (p = 0.007). Our findings indicate that PTGS2 rs5275T/C may be a candidate genetic marker for gastric cancer susceptibility. 22385256 97 111 gastric cancer Disease D013274 22385256 0 16 Cyclooxygenase-2 Gene 5743 22385256 18 23 COX-2 Gene 5743 22385256 59 73 carcinogenesis Disease D063646 22385256 85 97 inflammation Disease D007249 22385256 150 155 tumor Disease D009369 22385256 189 194 COX-2 Gene 5743 22385256 223 230 cancers Disease D009369 22385256 242 256 gastric cancer Disease D013274 22385256 258 263 COX-2 Gene 5743 22385256 278 315 prostaglandin endoperoxide synthase 2 Gene 5743 22385256 317 322 PTGS2 Gene 5743 22385256 391 396 PTGS2 Gene 5743 22385256 415 429 gastric cancer Disease D013274 22385256 507 521 gastric cancer Disease D013274 22385256 658 663 PTGS2 Gene 5743 22385256 689 703 gastric cancer Disease D013274 22385256 832 846 gastric cancer Disease D013274 22385256 976 983 females Environment 5743-D013274 22385256 1042 1052 nonsmokers Environment 5743-D001943 22385256 1177 1184 smoking Environment 5743-D001943 22385256 1192 1206 gastric cancer Disease D013274 22385256 1252 1257 PTGS2 Gene 5743 22385256 1306 1320 gastric cancer Disease D013274 27270564|t|Gene-environment interaction between the MMP9 C-1562T promoter variant and cigarette smoke in the pathogenesis of chronic obstructive pulmonary disease. 27270564|t|The aetiology of chronic obstructive pulmonary disease (COPD) is complex. While cigarette smoking is a well-established cause of COPD, a myriad of assessed genetic factors has given conflicting data. Since gene-environment interactions are thought to be implicated in aetiopathogenesis of COPD, we aimed to examine the matrix metalloproteinase (MMP) 9 C-1562T (rs3918242) functional variant and cigarette smoke in the pathogenesis of this disease. The distribution of the MMP9 C-1562T variant was analyzed in COPD patients and controls with normal pulmonary function from Serbia. Interaction between the C-1562T genetic variant and cigarette smoking was assessed using a case-control model. The response of the C-1562T promoter variant to cigarette smoke condensate (CSC) exposure was examined using a dual luciferase reporter assay. The frequency of T allele carriers was higher in the COPD group than in smoker controls (38.4% vs. 20%; OR = 2.7, P = 0.027). Interaction between the T allele and cigarette smoking was identified in COPD occurrence (OR = 4.38, P = 0.005) and severity (P = 0.001). A functional analysis of the C-1562T variant demonstrated a dose-dependent and allele-specific response (P < 0.01) to CSC. Significantly higher MMP9 promoter activity following CSC exposure was found for the promoter harboring the T allele compared to the promoter harboring the C allele (P < 0.05). Our study is the first to reveal an interaction between the MMP9-1562T allele and cigarette smoke in COPD, emphasising gene-environment interactions as a possible cause of lung damage in the pathogenesis of COPD. Environ. Mol. Mutagen. 57:447-454, 2016. (c) 2016 Wiley Periodicals, Inc. 27270564 41 45 MMP9 Gene 4318 27270564 75 90 cigarette smoke Environment 4318-D029424 27270564 114 151 chronic obstructive pulmonary disease Disease D029424 27270564 17 54 chronic obstructive pulmonary disease Disease D029424 27270564 56 60 COPD Disease D029424 27270564 129 133 COPD Disease D029424 27270564 289 293 COPD Disease D029424 27270564 472 476 MMP9 Gene 4318 27270564 509 513 COPD Disease D029424 27270564 887 891 COPD Disease D029424 27270564 997 1014 cigarette smoking Environment 4318-D029424 27270564 1033 1037 COPD Disease D029424 27270564 1242 1246 MMP9 Gene 4318 27270564 1458 1462 MMP9 Gene 4318 27270564 1480 1495 cigarette smoke Environment 4318-D029424 27270564 1499 1503 COPD Disease D029424 27270564 1570 1581 lung damage Disease D055370 27270564 1605 1609 COPD Disease D029424 21132382|t|APE1 Asp148Glu gene polymorphism and lung cancer risk: a meta-analysis. 21132382|t|Many studies have examined the association between the APE1 T1349G (Asp148Glu) gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed, Embase, Web of Science, and CNKI database was searched for case-control studies published up to June 2010. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, ten studies, comprising 2,696 lung cancer cases and 3,948 controls were included. Overall, for the G allele carriers (TG + GG) versus homozygote TT, the pooled OR was 1.037 (95% CI = 0.928-1.159 P = 0.001 for heterogeneity), for GG versus TT the pooled OR was 0.997 (95% CI = 0.861-1.154 P = 0.005 for heterogeneity). In the stratified analysis by ethnicity, significantly risks were not found among Asians or Caucasians. However, in the subgroup analyses by smoking status, significantly risks were found among smokers not in non-smokers. This meta-analysis suggested that the APE1 T1349G (Asp148Glu) polymorphism was not associated with lung cancer risk among Asians or Caucasians. But, the APE1 G allele was an increased risk factor for developing lung cancer among smokers. 21132382 0 4 APE1 Gene 328 21132382 37 48 lung cancer Disease D008175 21132382 55 59 APE1 Gene 328 21132382 102 113 lung cancer Disease D008175 21132382 521 532 lung cancer Disease D008175 21132382 1003 1010 smokers Environment 328-D008175 21132382 1069 1073 APE1 Gene 328 21132382 1130 1141 lung cancer Disease D008175 21132382 1184 1188 APE1 Gene 328 21132382 1242 1253 lung cancer Disease D008175 21132382 1260 1267 smokers Environment 328-D008175 19487392|t|Serotonin transporter gene (SLC6A4) promoter polymorphisms and the susceptibility to posttraumatic stress disorder in the general population. 19487392|t|OBJECTIVE: There has been debate whether polymorphisms within the serotonin transporter-linked polymorphic region (5-HTTLPR) moderate susceptibility to posttraumatic stress disorder (PTSD). The authors investigated 5-HTTLPR genotypes and their interaction with the number of traumatic events in the prediction of PTSD in a general population sample. METHOD: Analyses were based on data from 3,045 subjects who participated in the Study of Health in Pomerania. All participants were assessed with the PTSD module of the Structured Clinical Interview for DSM-IV. The short (S)/long (L) polymorphism of 5-HTTLPR (rs4795541) and the A-G polymorphism (rs25531) were genotyped. RESULTS: Among the participants, 1,663 had been exposed to at least one traumatic event, and 67 (4.0%) developed PTSD. Among those who had experienced less than three traumatic events, the lifetime prevalence of PTSD was 2.6%, 3.5%, and 4.3% for those with zero, one, and two L(A) alleles, respectively, but the lifetime prevalence was 0%, 7.3%, and 19.6%, respectively, among those with three or more traumatic experiences. This finding suggests that there is an additive excess risk for frequent trauma in the L(A)/L(A) genotype, which was confirmed by the relative excess risk due to interaction (RERI). In allelic analysis, RERI was 3.3. Thus, the odds ratio for PTSD in L(A) allele carriers exposed to three or more traumas was 3.3 times higher as a result of the interaction between PTSD and the L(A) allele. CONCLUSIONS: An additive gene-environment interaction with the high expression L(A) allele of 5-HTTLPR and frequent trauma in PTSD was found. The attributable proportion indicated that more than 60% of all L(A) allele carriers who were exposed to three or more traumas developed PTSD as a result of an interaction between genotype and exposure. 19487392 0 21 Serotonin transporter Gene 6532 19487392 28 34 SLC6A4 Gene 6532 19487392 85 114 posttraumatic stress disorder Disease D013313 19487392 66 87 serotonin transporter Gene 6532 19487392 115 123 5-HTTLPR Gene 6532 19487392 152 181 posttraumatic stress disorder Disease D013313 19487392 183 187 PTSD Disease D013313 19487392 215 223 5-HTTLPR Gene 6532 19487392 275 284 traumatic Disease D014947 19487392 313 317 PTSD Disease D013313 19487392 500 504 PTSD Disease D013313 19487392 600 608 5-HTTLPR Gene 6532 19487392 744 753 traumatic Disease D014947 19487392 785 789 PTSD Disease D013313 19487392 823 855 less than three traumatic events Environment 6532-D013313 19487392 839 848 traumatic Disease D014947 19487392 884 888 PTSD Disease D013313 19487392 1060 1095 three or more traumatic experiences Environment 6532-D013313 19487392 1074 1083 traumatic Disease D014947 19487392 1161 1176 frequent trauma Environment 6532-D013313 19487392 1170 1176 trauma Disease D014947 19487392 1339 1343 PTSD Disease D013313 19487392 1379 1400 three or more traumas Environment 6532-D013313 19487392 1393 1400 traumas Disease D014947 19487392 1461 1465 PTSD Disease D013313 19487392 1581 1589 5-HTTLPR Gene 6532 19487392 1594 1609 frequent trauma Environment 6532-D013313 19487392 1603 1609 trauma Disease D014947 19487392 1613 1617 PTSD Disease D013313 19487392 1734 1755 three or more traumas Environment 6532-D013313 19487392 1748 1755 traumas Disease D014947 19487392 1766 1770 PTSD Disease D013313 19176458|t|Estimated risk of radiation-induced breast cancer from mammographic screening for young BRCA mutation carriers. 19176458|t|BRCA mutation carriers are recommended to start mammographic screening for breast cancer as early as age 25-30 years. We used an excess relative risk model (based on a pooled analysis of three cohorts with 7600 subjects who received radiation exposure) to estimate the lifetime risk of radiation-induced breast cancer from five annual mammographic screenings in young (<40 years) BRCA mutation carriers. We then estimated the reduction in breast cancer mortality required to outweigh the radiation risk. Breast cancer rates for mutation carriers were based on a pooled analysis of 22 pedigree studies with 8139 subjects. For BRCA1 mutation carriers, the estimated lifetime risk of radiation-induced breast cancer mortality per 10,000 women resulting from annual mammography was 26 (95% confidence interval [CI] = 14 to 49) for screening at age 25-29 years, 20 (95% CI = 11 to 39) for screening at age 30-34 years, and 13 (95% CI = 7 to 23) for screening at age 35-39 years. To outweigh these risks, screening would have to reduce breast cancer mortality by 51% (95% CI = 27% to 96%) at age 25-29 years, by 12% (95% CI = 6% to 23%) at age 30-34 years, and by 4% (95% CI = 2% to 7%) at age 35-39 years; estimates were similar for BRCA2 mutation carriers. If we assume that the mortality reduction from mammography is 15%-25% or less for young women, these results suggest that there would be no net benefit from annual mammographic screening of BRCA mutation carriers at age 25-29 years; the net benefit would be zero or small at age 30-34 years, but there should be some net benefit at age 35 or older. These results depend on a number of assumptions due to the absence of empiric data. The impact of varying these assumptions was therefore examined. 19176458 36 49 breast cancer Disease D001943 19176458 88 92 BRCA Gene 672 19176458 0 4 BRCA Gene 672 19176458 75 88 breast cancer Disease D001943 19176458 304 317 breast cancer Disease D001943 19176458 380 384 BRCA Gene 672 19176458 439 452 breast cancer Disease D001943 19176458 504 517 Breast cancer Disease D001943 19176458 625 630 BRCA1 Gene 672 19176458 699 712 breast cancer Disease D001943 19176458 897 912 age 35-39 years Environment 672-D001943 19176458 1030 1043 breast cancer Disease D001943 19176458 1184 1199 age 35-39 years Environment 675-D001943 19176458 1228 1233 BRCA2 Gene 675 19176458 1443 1447 BRCA Gene 672 19176458 1585 1600 age 35 or older Environment 672-D001943 12869766|t|Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. 12869766|t|In a prospective-longitudinal study of a representative birth cohort, we tested why stressful experiences lead to depression in some people but not in others. A functional polymorphism in the promoter region of the serotonin transporter (5-HT T) gene was found to moderate the influence of stressful life events on depression. Individuals with one or two copies of the short allele of the 5-HT T promoter polymorphism exhibited more depressive symptoms, diagnosable depression, and suicidality in relation to stressful life events than individuals homozygous for the long allele. This epidemiological study thus provides evidence of a gene-by-environment interaction, in which an individual's response to environmental insults is moderated by his or her genetic makeup. 12869766 13 24 life stress Environment 6532-D003866 12869766 28 38 depression Disease D003866 12869766 76 81 5-HTT Gene 6532 12869766 114 124 depression Disease D003866 12869766 215 244 serotonin transporter (5-HT T Gene 6532 12869766 290 311 stressful life events Environment 6532-D003866 12869766 315 325 depression Disease D003866 12869766 433 452 depressive symptoms Disease D003866 12869766 466 476 depression Disease D003866 12869766 509 530 stressful life events Environment 6532-D003866 20084546|t|IGFBP3 A-202C polymorphism and breast cancer susceptibility: a meta-analysis involving 33,557 cases and 45,254 controls. 20084546|t|Published data on the association between insulin-like growth factor binding protein 3 (IGFBP3) A-202C polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of 27 studies including 33,557 cases and 45,254 controls were involved in this meta-analysis. Overall, significantly elevated breast cancer risk was associated with IGFBP3 C allele when all studies were pooled into the meta-analysis (CC vs. AA: OR = 1.06, 95% CI = 1.02-1.11; dominant model: OR = 1.04, 95% CI = 1.00-1.07). In the subgroup analysis by ethnicity, significantly increased risk was found for Caucasians (AC vs. AA: OR = 1.04, 95% CI = 1.00-1.08; CC vs. AA: OR = 1.05, 95% CI = 1.01-1.10; dominant model: OR = 1.04, 95% CI = 1.00-1.08) and Asians (CC vs. AA: OR = 1.35, 95% CI = 1.02-1.78; recessive model: OR = 1.38, 95% CI = 1.05-1.82). When stratified by study design, statistically significantly elevated risk was found among population-based studies (CC vs. AA: OR = 1.06, 95% CI = 1.01-1.11; dominant model: OR = 1.03, 95% CI = 1.00-1.07). In the subgroup analysis by menopausal status, no statistically significantly increased risk was found among premenopausal or postmenopausal women. In conclusion, this meta-analysis suggests that the IGFBP3 C allele is a low-penetrant risk factor for developing breast cancer. 20084546 0 6 IGFBP3 Gene 3486 20084546 31 44 breast cancer Disease D001943 20084546 42 86 insulin-like growth factor binding protein 3 Gene 3486 20084546 88 94 IGFBP3 Gene 3486 20084546 120 133 breast cancer Disease D001943 20084546 464 477 breast cancer Disease D001943 20084546 503 509 IGFBP3 Gene 3486 20084546 744 754 Caucasians Environment 3486-D001943 20084546 891 897 Asians Environment 3486-D001943 20084546 1397 1403 IGFBP3 Gene 3486 20084546 1459 1472 breast cancer Disease D001943 17680641|t|Polymorphic variants in alpha-methylacyl-CoA racemase and prostate cancer. 17680641|t|BACKGROUND: Alpha-methylacyl-CoA racemase (AMACR), which prepares branched chain fatty acids to be metabolized for energy and is implicated in the activation of the COX-inhibiting form of ibuprofen, is overexpressed in prostate cancer and its precursor lesions. Significant differences in AMACR allele frequencies have been reported for hereditary prostate cancer (HPC), but the relevance of AMACR in the context of its substrates have not been studied. METHODS: We conducted a nested case-control study of 1,318 prostate cancer cases and 1,842 controls from the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Five non-synonymous (nsSNP) and two intronic AMACR polymorphisms were genotyped. Conditional logistic regression models were used to evaluate the associations between the genetic variants and prostate cancer. RESULTS: Overall, prostate cancer was not related to AMACR gene variants; however, risks for prostate cancer were significantly reduced among regular ibuprofen users who carried allele variants at four nsSNP loci (M9V, D175G, S201L, and K277E; all P(trend) < 0.05) or carried the TGTGCG haplotype (OR = 0.65; 95% CI 0.44-0.97). No AMACR-related associations were noted among nonregular ibuprofen users (all P(interaction) > 0.33). CONCLUSION: AMACR gene variants were unrelated to prostate cancer overall in this study. The protective associations observed among ibuprofen users suggest that AMACR gene variants may enhance the chemopreventive effects of ibuprofen on prostate cancer risk. 17680641 24 53 alpha-methylacyl-CoA racemase Gene 23600 17680641 24 53 alpha-methylacyl-CoA racemase Disease D015417 17680641 58 73 prostate cancer Disease D011471 17680641 12 41 Alpha-methylacyl-CoA racemase Gene 23600 17680641 12 41 Alpha-methylacyl-CoA racemase Disease D015417 17680641 43 48 AMACR Gene 23600 17680641 43 48 AMACR Disease D015417 17680641 219 234 prostate cancer Disease D011471 17680641 289 294 AMACR Gene 23600 17680641 289 294 AMACR Disease D015417 17680641 337 363 hereditary prostate cancer Disease C537243 17680641 365 368 HPC Disease C537243 17680641 392 397 AMACR Gene 23600 17680641 392 397 AMACR Disease D015417 17680641 513 528 prostate cancer Disease D011471 17680641 600 610 Colorectal Disease D015179 17680641 631 637 Cancer Disease D009369 17680641 700 705 AMACR Gene 23600 17680641 700 705 AMACR Disease D015417 17680641 847 862 prostate cancer Disease D011471 17680641 882 897 prostate cancer Disease D011471 17680641 917 922 AMACR Gene 23600 17680641 917 922 AMACR Disease D015417 17680641 957 972 prostate cancer Disease D011471 17680641 1014 1037 regular ibuprofen users Environment 23600-D011471 17680641 1203 1208 AMACR Gene 23600 17680641 1203 1208 AMACR Disease D015417 17680641 1315 1320 AMACR Gene 23600 17680641 1315 1320 AMACR Disease D015417 17680641 1353 1368 prostate cancer Disease D011471 17680641 1435 1450 ibuprofen users Environment 23600-D011471 17680641 1464 1469 AMACR Gene 23600 17680641 1464 1469 AMACR Disease D015417 17680641 1496 1536 the chemopreventive effects of ibuprofen Environment 23600-D011471 17680641 1540 1555 prostate cancer Disease D011471 19706847|t|Vitamin D related genes, CYP24A1 and CYP27B1, and colon cancer risk. 19706847|t|Genetic association studies investigating the role of vitamin D in colon cancer have primarily focused on the vitamin D receptor (VDR), with limited data available for other genes in the vitamin D pathway, including vitamin D activating enzyme 1-alpha hydroxylase (CYP27B1) and vitamin D deactivating enzyme 24-alpha hydroxylase (CYP24A1). We evaluated whether 12 tagging single nucleotide polymorphisms (SNP) in CYP24A1, identified by resequencing the gene in 32 Caucasian samples, and 1 SNP in CYP27B1 were associated with colon cancer risk. In addition, we evaluated whether these two genes modify associations between colon cancer on the one hand and total vitamin D intake and UV-weighted sun exposure on the other, as well as other variants in VDR. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the association between polymorphisms and haplotypes in CYP27B1 and CYP24A1 in a multicenter population-based case-control study of 1,600 cases and 1,949 controls. The CYP24A1 polymorphism IVS4-66T > G showed a statistically significant association with risk of colon cancer overall, particularly for proximal colon cancer. When stratified by anatomic site, we also found statistically significant associations for three CYP24A1 polymorphisms with risk of distal colon cancer (IVS4 + 1653C > T: OR for CT/TT versus CC, 0.81; 95% CI, 0.68-0.96; IVS9 + 198T > C: OR for CC versus TT, 1.33; 95% CI, 1.03-1.73; and within whites only: +4125bp 3' of STPC > G: OR for GG versus CC, 1.44; 95% CI, 1-2.05). In addition, a possible interaction between CYP27B1 and UV-weighted sun exposure with proximal colon cancer was observed. As this is the first study to evaluate these genes in relation to colon cancer, additional studies are needed to confirm these results. 19706847 25 32 CYP24A1 Gene 1591 19706847 37 44 CYP27B1 Gene 1594 19706847 50 62 colon cancer Disease D003110 19706847 67 79 colon cancer Disease D003110 19706847 110 128 vitamin D receptor Gene 7421 19706847 130 133 VDR Gene 7421 19706847 265 272 CYP27B1 Gene 1594 19706847 330 337 CYP24A1 Gene 1591 19706847 413 420 CYP24A1 Gene 1591 19706847 496 503 CYP27B1 Gene 1594 19706847 525 537 colon cancer Disease D003110 19706847 622 634 colon cancer Disease D003110 19706847 750 753 VDR Gene 7421 19706847 926 933 CYP27B1 Gene 1594 19706847 938 945 CYP24A1 Gene 1591 19706847 1038 1045 CYP24A1 Gene 1591 19706847 1132 1144 colon cancer Disease D003110 19706847 1180 1192 colon cancer Disease D003110 19706847 1291 1298 CYP24A1 Gene 1591 19706847 1326 1345 distal colon cancer Environment 1591-D003110 19706847 1333 1345 colon cancer Disease D003110 19706847 1613 1620 CYP27B1 Gene 1594 19706847 1625 1649 UV-weighted sun exposure Environment 1591-D003110 19706847 1664 1676 colon cancer Disease D003110 19706847 1757 1769 colon cancer Disease D003110 17301261|t|Dietary folate intake, MTHFR genetic polymorphisms, and the risk of endometrial cancer among Chinese women. 17301261|t|Folate plays an important role in carcinogenesis. The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), encoded by the MTHFR gene, is involved in this process. We investigated both the independent and joint effects of dietary folate and other methyl-related nutrients, as well as three polymorphisms of MTHFR (677C>T, 1298A>C, and 1793G>A), on endometrial cancer risk in a population-based case-control study. Between 1997 and 2003, 1,204 newly diagnosed endometrial cancer cases and 1,212 controls were recruited among women between the ages of 30 and 69 years in urban Shanghai, China. Information on dietary intake of folate and other methyl-related nutrients, including vitamin B2 (riboflavin), vitamin B6, vitamin B12, and methionine, was derived from a validated food frequency questionnaire. Genotyping was completed on 1,041 cases and 1,030 controls for MTHFR 677C>T (rs1801133), 1298A>C (rs1801131), and 1793 G>A (rs2274967) [corrected] Haplotype estimation of the three single-nucleotide polymorphisms was performed using PHASE software. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate associations of nutrients, MTHFR genotypes, and haplotypes with endometrial cancer risk. A significant inverse association between dietary folate intake and endometrial cancer risk was observed among all subjects and non-B vitamin supplement users. The greatest reduction in endometrial cancer risk was observed among non-users of supplements in the highest quartile of dietary folate intake (OR, 0.5; 95% CI, 0.4-0.7) as compared with those in the lowest quartile. Dietary intake of folate cofactors (methionine, vitamin B2, vitamin B6, and vitamin B12) was not related to risk of endometrial cancer. No association was observed between endometrial cancer and the MTHFR 677C>T, 1298 A>C, and 1793G>A polymorphisms or derived haplotypes. Among non-users of supplements, however, the 1298C and 1793A alleles were associated with a lower risk of endometrial cancer among women with high dietary folate intake but related to a higher risk among those with low dietary folate intake (P(interaction) = 0.08 and 0.03, respectively). Further analysis showed that the lowest risk (OR, 0.6; 95% CI, 0.4-1.1) was among women with the 1298C allele and the highest intake of both folate and riboflavin (P(interaction) = 0.04). A similar association was observed for the 1793A allele (P(interaction) = 0.03). Our findings suggest that folate intake may decrease the risk of endometrial cancer and modify the effect of MTHFR polymorphisms on risk. 17301261 23 28 MTHFR Gene 4524 17301261 68 86 endometrial cancer Disease D016889 17301261 34 48 carcinogenesis Disease D063646 17301261 61 101 5,10-methylenetetrahydrofolate reductase Gene 4524 17301261 103 108 MTHFR Gene 4524 17301261 126 131 MTHFR Gene 4524 17301261 310 315 MTHFR Gene 4524 17301261 351 369 endometrial cancer Disease D016889 17301261 462 480 endometrial cancer Disease D016889 17301261 869 874 MTHFR Gene 4524 17301261 1165 1170 MTHFR Gene 4524 17301261 1202 1220 endometrial cancer Disease D016889 17301261 1295 1313 endometrial cancer Disease D016889 17301261 1413 1431 endometrial cancer Disease D016889 17301261 1720 1738 endometrial cancer Disease D016889 17301261 1776 1794 endometrial cancer Disease D016889 17301261 1803 1808 MTHFR Gene 4524 17301261 1982 2000 endometrial cancer Disease D016889 17301261 2018 2044 high dietary folate intake Environment 4524-D016889 17301261 2091 2116 low dietary folate intake Environment 4524-D016889 17301261 2279 2327 the highest intake of both folate and riboflavin Environment 4524-D016889 17301261 2460 2473 folate intake Environment 4524-D016889 17301261 2499 2517 endometrial cancer Disease D016889 17301261 2543 2548 MTHFR Gene 4524 20802237|t|Genetic variations in TERT-CLPTM1L genes and risk of squamous cell carcinoma of the head and neck. 20802237|t|Single-nucleotide polymorphisms (SNPs) of TERT-rs2736098 (C > T) and CLPTM1L-rs401681(C > T) at the 5p15.33 locus are significantly associated with cancer risk as reported in genome-wide association studies (GWAS), but there are no reported studies for squamous cell carcinoma of the head and neck (SCCHN). In a case-control study of 1079 SCCHN cases and 1115 cancer-free controls of non-Hispanic whites who were frequency matched by age and sex, we genotyped for these two SNPs and assessed their associations with SCCHN risk. Compared with the CC genotypes of each polymorphism, the associations of a slightly reduced risk of SCCHN with the variant genotypes of CT + TT of both polymorphisms were approaching statistical significance [Odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.76-1.08 for TERT-rs2736098 and OR = 0.86, 95% CI = 0.71-1.04 for CLPTM1L-rs401681, respectively]. When the two SNPs were combined, the variant genotypes of the two SNPs were significantly associated a moderately reduced risk of SCCHN (OR = 0.82, 95% CI = 0.67-0.99), and the number of variant genotypes was associated with a significantly reduced risk in a dose-response manner (P = 0.028). Furthermore, the reduced risk was more pronounced in ever smokers, ever drinkers and patients with oropharyngeal cancer. Our results suggested that these two SNPs at the 5p15.33 locus may be associated with a reduced risk of SCCHN, particularly for their combined effect. Although we added additional evidence for the association of the two SNPs with cancer risk as reported in GWAS, additional studies are needed to replicate our findings. 20802237 22 26 TERT Gene 7015 20802237 27 34 CLPTM1L Gene 81037 20802237 53 97 squamous cell carcinoma of the head and neck Disease C535575 20802237 42 46 TERT Gene 7015 20802237 69 76 CLPTM1L Gene 81037 20802237 148 154 cancer Disease D009369 20802237 253 297 squamous cell carcinoma of the head and neck Disease C535575 20802237 299 304 SCCHN Disease C535575 20802237 339 344 SCCHN Disease C535575 20802237 360 366 cancer Disease D009369 20802237 516 521 SCCHN Disease C535575 20802237 628 633 SCCHN Disease C535575 20802237 806 810 TERT Gene 7015 20802237 859 866 CLPTM1L Gene 81037 20802237 1022 1027 SCCHN Disease C535575 20802237 1238 1250 ever smokers Environment 81037-C535575 20802237 1238 1250 ever smokers Environment 7015-C535575 20802237 1252 1265 ever drinkers Environment 81037-C535575 20802237 1252 1265 ever drinkers Environment 7015-C535575 20802237 1284 1304 oropharyngeal cancer Disease D009959 20802237 1284 1304 oropharyngeal cancer Environment 81037-C535575 20802237 1284 1304 oropharyngeal cancer Environment 7015-C535575 20802237 1410 1415 SCCHN Disease C535575 20802237 1536 1542 cancer Disease D009369 19754661|t|5-HTTLPR moderates the effect of relational peer victimization on depressive symptoms in adolescent girls. 19754661|t|BACKGROUND: Relational peer victimization is associated with internalizing symptoms. Compared to boys, girls are more likely to be both relationally victimized by peers and distressed by the victimization. While previous studies have reported that a functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) moderates the effect of stressful life events on depressive symptoms, the present study is the first to evaluate the interaction of this polymorphism with relational peer victimization to predict level of depressive symptoms in young girls. METHODS: Participants were 78 girls ages 10 to 14 who had no current or past Axis I disorder. Girls were genotyped for 5-HTTLPR; peer victimization was assessed with the Social Experiences Questionnaire, and depressive symptoms with the Children's Depression Inventory. RESULTS: The 5-HTTLPR polymorphism alone did not predict level of depressive symptoms; the interaction of 5-HTTLPR and relational peer victimization, however, was a significant predictor of depressive symptoms. Follow-up analyses indicated that peer victimization significantly predicted level of depressive symptoms only for girls who were homozygous for the short allele, and not for girls homozygous for the long allele or who were heterozygous for the short and long alleles. CONCLUSIONS: The findings support the diathesis-stress model of depression: having two 5-HTTLPR short alleles confers vulnerability to depressive symptoms in adolescent girls when they experience relational peer victimization. These findings also suggest that relational peer victimization, at least for girls with genetic vulnerability, is a significant source of stress and should be recognized in the monitoring and prevention of bullying. 19754661 0 8 5-HTTLPR Gene 6532 19754661 33 62 relational peer victimization Environment 6532-D003866 19754661 66 85 depressive symptoms Disease D003866 19754661 304 325 serotonin transporter Gene 6532 19754661 332 340 5-HTTLPR Gene 6532 19754661 366 387 stressful life events Environment 6532-D003866 19754661 391 410 depressive symptoms Disease D003866 19754661 547 566 depressive symptoms Disease D003866 19754661 660 675 Axis I disorder Disease 1 19754661 702 710 5-HTTLPR Gene 6532 19754661 791 810 depressive symptoms Disease D003866 19754661 831 841 Depression Disease D003866 19754661 866 874 5-HTTLPR Gene 6532 19754661 919 938 depressive symptoms Disease D003866 19754661 959 967 5-HTTLPR Gene 6532 19754661 972 1001 relational peer victimization Environment 6532-D003866 19754661 1043 1062 depressive symptoms Disease D003866 19754661 1098 1116 peer victimization Environment 6532-D003866 19754661 1150 1169 depressive symptoms Disease D003866 19754661 1371 1380 diathesis Disease D004198 19754661 1397 1407 depression Disease D003866 19754661 1420 1428 5-HTTLPR Gene 6532 19754661 1468 1487 depressive symptoms Disease D003866 19754661 1529 1558 relational peer victimization Environment 6532-D003866 19298002|t|Genetic polymorphism in chemokine CCL22 and susceptibility to Helicobacter pylori infection-related gastric carcinoma. 19298002|t|BACKGROUND: Gastric carcinoma is widely considered to be related to Helicobacter pylori infection, and the chemokine (C-C motif) ligand 22 (CCL22) plays an important role in suppressing immune responses against H. pylori and tumor cells. In this study, the authors examined the association between single nucleotide polymorphisms (SNPs) in the CCL22 gene and the risk of gastric carcinoma. METHODS: Information on SNPs in the CCL22 coding region was obtained from the HapMap Project database. Genotypes were determined in a case-control cohort that consisted of 1001 patients with gastric carcinoma and 1066 controls, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were computed by using a logistic regression model. Serum H. pylori antibody levels were measured by using an enzyme-linked immunosorbent assay. RESULTS: The 16C-->A SNP (reference SNP no. 4359426) in exon 1 of the CCL22 gene, which causes a 2 aspartate (2Asp) to 2 alanine (2Ala) substitution in the CCL22 protein, was associated with a significantly increased risk of gastric carcinoma. Individuals who were homozygous for the Ala/Ala genotype had an OR of 2.27 (95% CI, 1.28-4.02) compared with individuals who had the Asp/Asp genotype. Stratification analysis indicated that the association was more pronounced among men (OR, 2.64; 95% CI, 1.29-5.41) and among younger individuals (OR, 2.85; 95% CI, 1.36-5.96) compared with women and older individuals. Moreover, a multiplicative joint effect between the CCL22 SNP and H. pylori infection that intensified the risk was observed (OR for the presence of both Ala/Ala genotype and H. pylori infection, 18.37; 95% CI, 2.30-146.67). CONCLUSIONS: The results from this study suggested that the CCL22 polymorphism is associated with an increase risk of developing H. pylori infection-related gastric carcinoma. 19298002 34 39 CCL22 Gene 6367 19298002 82 91 infection Disease D007239 19298002 108 117 carcinoma Disease D002277 19298002 20 29 carcinoma Disease D002277 19298002 88 97 infection Disease D007239 19298002 140 145 CCL22 Gene 6367 19298002 225 230 tumor Disease D009369 19298002 344 349 CCL22 Gene 6367 19298002 371 388 gastric carcinoma Disease 1 19298002 426 431 CCL22 Gene 6367 19298002 581 598 gastric carcinoma Disease 1 19298002 893 898 CCL22 Gene 6367 19298002 979 984 CCL22 Gene 6367 19298002 1048 1065 gastric carcinoma Disease 1 19298002 1299 1302 men Environment 6367-1 19298002 1343 1362 younger individuals Environment 6367-1 19298002 1488 1493 CCL22 Gene 6367 19298002 1502 1520 H.pylori infection Environment 6367-1 19298002 1511 1520 infection Disease D007239 19298002 1610 1628 H.pylori infection Environment 6367-1 19298002 1619 1628 infection Disease D007239 19298002 1719 1724 CCL22 Gene 6367 19298002 1788 1806 H.pylori infection Environment 6367-1 19298002 1797 1806 infection Disease D007239 19298002 1823 1832 carcinoma Disease D002277 11888908|t|Gene-environment interaction for the ERCC2 polymorphisms and cumulative cigarette smoking exposure in lung cancer. 11888908|t|Excision repair cross-complementing group 2 (ERCC2), a major DNA repair protein, is involved in nucleotide excision repair and basal transcription. The ERCC2 polymorphisms have been associated with altered DNA repair capacity. We investigated two ERCC2 polymorphisms, Asp312Asn and Lys751Gln, in 1092 Caucasian lung cancer patients and 1240 spouse and friend controls. The results were analyzed using generalized additive models and logistic regression, adjusting for relevant covariates. The overall adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.47 (95% CI, 1.1-2.0) for the Asp312Asn polymorphism (Asn/Asn versus Asp/Asp) and 1.06 (95% CI, 0.8-1.4) for the Lys751Gln polymorphism (Gln/Gln versus Lys/Lys). Gene-smoking interaction analyses revealed that the adjusted ORs for each of the two polymorphisms decreased significantly as pack-years increased. When comparing individuals with Asn/Asn + Gln/Gln versus individuals with Asp/Asp + Lys/Lys, the fitted ORs (95% CIs) were 2.56 (95% CI, 1.3-5.0) in nonsmokers and 0.69 (95% CI, 0.4-1.2) in heavy smokers (80 pack-years; P < 0.01 for the interaction term). Consistent and robust results were found when models incorporated different definitions of cumulative cigarette smoking. A stronger gene-smoking interaction was observed for the Asp312Asn polymorphism than for the Lys751Gln polymorphism. In conclusion, cumulative cigarette smoking modifies the associations between ERCC2 polymorphisms and lung cancer risk. 11888908 37 42 ERCC2 Gene 2068 11888908 61 98 cumulative cigarette smoking exposure Environment 2068-D008175 11888908 102 113 lung cancer Disease D008175 11888908 0 43 Excision repair cross-complementing group 2 Gene 2068 11888908 45 50 ERCC2 Gene 2068 11888908 61 79 DNA repair protein Gene 442459 11888908 152 157 ERCC2 Gene 2068 11888908 247 252 ERCC2 Gene 2068 11888908 311 322 lung cancer Disease D008175 11888908 857 877 pack-years increased Environment 2068-D008175 11888908 1069 1082 heavy smokers Environment 2068-D008175 11888908 1084 1097 80 pack-years Environment 2068-D008175 11888908 1226 1254 cumulative cigarette smoking Environment 2068-D008175 11888908 1388 1416 cumulative cigarette smoking Environment 2068-D008175 11888908 1451 1456 ERCC2 Gene 2068 11888908 1475 1486 lung cancer Disease D008175 21198273|t|Association of the 8473T>C cyclooxygenase-2 (COX-2) gene polymorphism with lung cancer risk in Asians. 21198273|t|OBJECTIVE: To evaluate the impact of the COX-2 gene 8473T>C polymorphism on lung cancer risk in Asians, we conducted a comprehensive meta-analysis. METHODS: A literature search was performed using PubMed and other databases before June 2010. We pooled studies according to the variants of 8473T>C and performed separate analyses according to ethnicity, histological type and smoking status, with attention to study quality and publication bias. RESULTS: A total of five case-control studies including 2,450 cases and 4,302 controls were available. Overall, individuals with the C allele had a reduced lung cancer risk compared with the TT genotype on global analysis (odds ratio [OR] =0.89, 95% confidence interval [CI] =0.81 to 0.97, P=0.01, I2 for heterogeneity =0%). Significant associations were also observed in subgroups of Asian populations (OR=0.84, 95% CI=0.72 to 0.98) when stratified by ethnicity, as well as for small cell lung cancer (OR=0.54, 95% CI=0.31 to 0.95) stratified by pathological type. CONCLUSIONS: Our results suggest the COX-2 gene is a factor for suffering from lung cancer, especially of small cell type among Asians. 21198273 27 43 cyclooxygenase-2 Gene 5743 21198273 45 50 COX-2 Gene 5743 21198273 75 86 lung cancer Disease D008175 21198273 41 46 COX-2 Gene 5743 21198273 76 87 lung cancer Disease D008175 21198273 601 612 lung cancer Disease D008175 21198273 830 847 Asian populations Environment 5743-D008175 21198273 924 946 small cell lung cancer Disease D055752 21198273 1048 1053 COX-2 Gene 5743 21198273 1090 1101 lung cancer Disease D008175 21198273 1139 1145 Asians Environment 5743-D008175 12844487|t|Cytochrome P450 1B1 gene polymorphisms and postmenopausal breast cancer risk. 12844487|t|Cytochrome P450 1B1 (CYP1B1) is active in the metabolism of estrogens to reactive catechols and of different procarcinogens. Several studies have investigated the relationship between genetic polymorphisms of CYP1B1 and breast cancer risk, however, with inconsistent results. We investigated such an association in postmenopausal Swedish women, with special emphasis on long-term menopausal hormone users, in a large population-based case-control study. We genotyped 1521 cases and 1498 controls for the CYP1B1 single nucleotide polymorphisms (SNPs) m2, m3 and m4 and reconstructed haplotypes. The frequencies of CYP1B1*1, CYP1B1*2, CYP1B1*3 and CYP1B1*4 alleles among controls were estimated to be 0.087, 0.293, 0.444 and 0.175, respectively. It thus appeared that very few haplotypes contained combinations of SNPs at two or three loci and that single SNP genotype data effectively represented haplotypes. Odds ratios (OR) and 95% confidence intervals (CI) were calculated from logistic regression models. We found no overall association between any CYP1B1 genotype and breast cancer risk. The data indicated, however, that women who had used menopausal hormones for 4 years or longer, and carried the CYP1B1*3/*3 genotype may be at increased risk of breast cancer, OR 2.0 (95% CI 1.1-3.5), compared with long-term users without this genotype. We explored the effect of CYP1B1 genotype on breast cancer risk in subgroups defined by body mass index, family history, smoking and catechol-O-methyl transferase genotype, but found no convincing evidence for interaction. In summary, our results strongly indicate that the studied CYP1B1 gene polymorphisms do not influence breast cancer risk overall but may modify the risk after long-term menopausal hormone use. 12844487 0 19 Cytochrome P450 1B1 Gene 1545 12844487 58 71 breast cancer Disease D001943 12844487 0 19 Cytochrome P450 1B1 Gene 1545 12844487 21 27 CYP1B1 Gene 1545 12844487 209 215 CYP1B1 Gene 1545 12844487 220 233 breast cancer Disease D001943 12844487 504 510 CYP1B1 Gene 1545 12844487 613 619 CYP1B1 Gene 1545 12844487 623 629 CYP1B1 Gene 1545 12844487 633 639 CYP1B1 Gene 1545 12844487 646 652 CYP1B1 Gene 1545 12844487 1052 1058 CYP1B1 Gene 1545 12844487 1072 1085 breast cancer Disease D001943 12844487 1145 1186 menopausal hormones for 4 years or longer Environment 1545-D001943 12844487 1204 1210 CYP1B1 Gene 1545 12844487 1253 1266 breast cancer Disease D001943 12844487 1372 1378 CYP1B1 Gene 1545 12844487 1391 1404 breast cancer Disease D001943 12844487 1628 1634 CYP1B1 Gene 1545 12844487 1671 1684 breast cancer Disease D001943 12844487 1728 1760 long-term menopausal hormone use Environment 1545-D001943 19064544|t|Recreational physical activity modifies the association between a common GH1 polymorphism and colorectal cancer risk. 19064544|t|UNLABELLED: Growth hormone may be associated with the development of colorectal cancer directly and/or indirectly via increased serum level of insulin-like growth factor (IGF-I). Regular physical activity can decrease insulin resistance and modulates IGF-I production. A common polymorphism in the GH1 gene, rs2665802, was previously shown to be associated with lower IGF-I levels and decreased colorectal cancer (CRC) risk. We investigated the association of this polymorphism and physical activity with colorectal cancer risk in a case-control study. METHODS: The analysis includes 3,041 (1,402 cases and 1,639 controls) participants in the Molecular Epidemiology of Colorectal Cancer study, a population-based case-control study in Northern Israel. Analysis was carried out separately in two sets. The first set included 1,248 subjects (625 cases, 623 controls), and the second validation set consisted of 1,793 subjects (777 cases, 1,016 controls). RESULTS: No association was found between the studied polymorphism and CRC risk. However, evaluation of gene environment interactions revealed an interaction between leisure time physical activity and the GH1 polymorphism, which was consistent in both sets (P(interaction) = 0.005). The genotype AA was associated with decreased risk of CRC among individuals who did not engage in any such activity (odds ratio, 0.76; 95% confidence interval, 0.52-0.98), whereas the same genotype was marginally associated with increased risk among individuals who reported physical activity (odds ratio, 1.38; 95% confidence interval, 0.98-1.94). CONCLUSIONS: We found that the A allele of the rs2665802 polymorphism is associated with reduced risk of CRC only among physically inactive individuals, indicating an interaction between physical activity and the growth hormone/IGF-I system. A replication of the observed findings and further investigation of the underlying mechanism is warranted. 19064544 0 30 Recreational physical activity Environment 2688-D015179 19064544 73 76 GH1 Gene 2688 19064544 94 111 colorectal cancer Disease D015179 19064544 12 26 Growth hormone Gene 2688 19064544 69 86 colorectal cancer Disease D015179 19064544 171 176 IGF-I Gene 3479 19064544 251 256 IGF-I Gene 3479 19064544 298 301 GH1 Gene 2688 19064544 368 373 IGF-I Gene 3479 19064544 395 412 colorectal cancer Disease D015179 19064544 414 417 CRC Disease D015179 19064544 505 522 colorectal cancer Disease D015179 19064544 669 686 Colorectal Cancer Disease D015179 19064544 1024 1027 CRC Disease D015179 19064544 1119 1149 leisure time physical activity Environment 2688-D015179 19064544 1158 1161 GH1 Gene 2688 19064544 1290 1293 CRC Disease D015179 19064544 1334 1351 any such activity Environment 2688-D015179 19064544 1511 1528 physical activity Environment 2688-D015179 19064544 1690 1693 CRC Disease D015179 19064544 1705 1736 physically inactive individuals Environment 2688-D015179 19064544 1772 1789 physical activity Environment 3479-D015179 19064544 1772 1789 physical activity Environment 2688-D015179 19064544 1851 1865 growth hormone Gene 2688 19064544 1866 1871 IGF-I Gene 3479 10903223|t|The effect of polymorphisms of the beta(2)-adrenergic receptor on the response to regular use of albuterol in asthma. 10903223|t|Inhaled beta-adrenergic agonists are the most commonly used medications for the treatment of asthma although there is evidence that regular use may produce adverse effects in some patients. Polymorphisms of the beta(2)-adrenergic receptor (beta(2)-AR) can affect regulation of the receptor. Smaller studies examining the effects of such polymorphisms on the response to beta-agonist therapy have produced inconsistent results. We examined whether polymorphisms at codon 16 (beta(2)-AR-16) and codon 27 (beta(2)-AR-27) of the beta(2)-AR might affect the response to regular versus as-needed use of albuterol by genotyping the 190 asthmatics who had participated in a trial examining the effects of regular versus as needed albuterol use. During the 16-wk treatment period there was a small decline in morning peak expiratory flow in patients homozygous for arginine at B(2)-AR-16 (Arg/Arg) who used albuterol regularly. This effect was magnified during a 4-wk run out period, during which all patients returned to using as-needed albuterol, so that by the end of the study Arg Arg patients who had regularly used albuterol had a morning peak expiratory flow 30. 5 +/- 12.1 L/min lower (p = 0.012) than Arg/Arg patients who had used albuterol on an as needed basis. There was no decline in peak flow with regular use of albuterol in patients who were homozygous for glycine at beta(2)-AR-16. Evening peak expiratory flow also declined in the Arg/Arg patients who used albuterol regularly but not in those who used albuterol on an as-needed basis. No significant differences in outcomes between regular and as-needed treatment were associated with polymorphisms at position 27 of the beta(2)-AR. No other differences in asthma outcomes that we investigated occurred in relation to these beta(2)-AR polymorphisms. Polymorphisms of the beta(2)-AR may influence airway responses to regular inhaled beta-agonist treatment. 10903223 35 62 beta(2)-adrenergic receptor Gene 154 10903223 82 106 regular use of albuterol Environment 154-D001249 10903223 110 116 asthma Disease D001249 10903223 93 99 asthma Disease D001249 10903223 211 238 beta(2)-adrenergic receptor Gene 154 10903223 240 250 beta(2)-AR Gene 154 10903223 474 484 beta(2)-AR Gene 154 10903223 503 513 beta(2)-AR Gene 154 10903223 525 535 beta(2)-AR Gene 154 10903223 898 917 albuterol regularly Environment 154-D001249 10903223 1080 1121 patients who had regularly used albuterol Environment 154-D001249 10903223 1375 1385 beta(2)-AR Gene 154 10903223 1448 1485 patients who used albuterol regularly Environment 154-D001249 10903223 1681 1691 beta(2)-AR Gene 154 10903223 1717 1723 asthma Disease D001249 10903223 1784 1794 beta(2)-AR Gene 154 10903223 1831 1841 beta(2)-AR Gene 154 26058915|t|Genetic loci for serum magnesium among African-Americans and gene-environment interaction at MUC1 and TRPM6 in European-Americans: the Atherosclerosis Risk in Communities (ARIC) study. 26058915|t|BACKGROUND: Low serum magnesium levels have been associated with multiple chronic diseases. The regulation of serum magnesium homeostasis is not well understood. A previous genome-wide association study (GWAS) of European ancestry (EA) populations identified nine loci for serum magnesium. No such study has been conducted in African-Americans, nor has there been an evaluation of the interaction of magnesium-associated SNPs with environmental factors. The goals of this study were to identify genetic loci associated with serum magnesium in an African-American (AA) population using both genome-wide and candidate region interrogation approaches and to evaluate gene-environment interaction for the magnesium-associated variants in both EA and AA populations. We conducted a GWAS of serum magnesium in 2737 AA participants of the Atherosclerosis Risk in Communities (ARIC) Study and interrogated the regions of the nine published candidate loci in these results. Literature search identified the influence of progesterone on MUC1 expression and insulin on TRPM6 expression. RESULTS: The GWAS approach in African-American participants identified a locus near MUC1 as genome-wide significant (rs2974937, beta=-0.013, p=6.1x10(-9)). The candidate region interrogation approach identified two of the nine loci previously discovered in EA populations as containing SNPs that were significantly associated in African-American participants (SHROOM3 and TRPM6). The index variants at these three loci together explained 2.8 % of the variance in serum magnesium concentration in ARIC African-American participants. On the test of gene-environment interaction in ARIC EA participants, the index variant at MUC1 had 2.5 times stronger association in postmenopausal women with progestin use (beta=-0.028, p=7.3x10(-5)) than in those without any hormone use (beta=-0.011, p=7.0x10(-8), p for interaction 0.03). At TRPM6, the index variant had 1.6 times stronger association in those with lower fasting insulin levels (<80 pmol/L: beta=-0.013, p=1.6x10(-7); >/=80 pmol/L: beta=-0.008, p=1.8x10(-2), p for interaction 0.03). CONCLUSIONS: We identified three loci that explained 2.8% of the variance in serum magnesium concentration in ARIC African-American participants. Following-up on functional studies of gene expression identified gene-environment interactions between progestin use and MUC1 and between insulin and TRPM6 on serum magnesium concentration in ARIC European-American participants. These results extend our understanding of the metabolism of serum magnesium. 26058915 93 97 MUC1 Gene 4582 26058915 102 107 TRPM6 Gene 140803 26058915 135 150 Atherosclerosis Disease D050197 26058915 74 90 chronic diseases Disease D002908 26058915 832 847 Atherosclerosis Disease D050197 26058915 1027 1031 MUC1 Gene 4582 26058915 1058 1063 TRPM6 Gene 140803 26058915 1160 1164 MUC1 Gene 4582 26058915 1436 1443 SHROOM3 Gene 57619 26058915 1448 1453 TRPM6 Gene 140803 26058915 1698 1702 MUC1 Gene 4582 26058915 1767 1780 progestin use Environment 4582-D050197 26058915 1903 1908 TRPM6 Gene 140803 26058915 1977 2005 lower fasting insulin levels Environment 140803-D050197 26058915 2361 2374 progestin use Environment 4582-D050197 26058915 2379 2383 MUC1 Gene 4582 26058915 2396 2403 insulin Environment 140803-D050197 26058915 2408 2413 TRPM6 Gene 140803 16234515|t|Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study. 16234515|t|PURPOSE: The purpose of this study was to estimate the extent of protection offered against breast cancer by prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations and to determine to what extent risk reduction varies with age at oophorectomy, age at diagnosis, and time elapsed since surgery. PATIENTS AND METHODS: We analyzed 1,439 patients with breast cancer and 1,866 matched controls derived from a registry of BRCA1 and BRCA2 carriers. We estimated odds ratios (ORs) of breast cancer for having had a bilateral oophorectomy, using conditional logistic regression, matched for parity and for oral contraceptive use. RESULTS: A previous history of oophorectomy was associated with a significant reduction in breast cancer risk of 56% for BRCA1 carriers (OR = 0.44; 95% CI, 0.29 to 0.66) and of 46% for BRCA2 carriers (OR = 0.57; 95% CI, 0.28 to 1.15). The risk reduction was greater if the oophorectomy was performed before age 40 (OR = 0.36; 95% CI, 0.20 to 0.64 for BRCA1 carriers) than after age 40 (OR = 0.53; 95% CI, 0.30 to 0.91). The protective effect was evident for 15 years post-oophorectomy (OR = 0.39; 95% CI, 0.26 to 0.57). CONCLUSION: Oophorectomy is an effective means of reducing the risk of breast cancer in carriers of BRCA1 mutations. The data suggest oophorectomy is protective in BRCA2 carriers as well, but needs to be confirmed in other studies. 16234515 0 13 Breast cancer Disease D001943 16234515 29 51 bilateral oophorectomy Environment 675-D001943 16234515 29 51 bilateral oophorectomy Environment 672-D001943 16234515 55 60 BRCA1 Gene 672 16234515 65 70 BRCA2 Gene 675 16234515 92 105 breast cancer Disease D001943 16234515 150 155 BRCA1 Gene 672 16234515 159 164 BRCA2 Gene 675 16234515 359 372 breast cancer Disease D001943 16234515 427 432 BRCA1 Gene 672 16234515 437 442 BRCA2 Gene 675 16234515 487 500 breast cancer Disease D001943 16234515 641 675 A previous history of oophorectomy Environment 675-D001943 16234515 641 675 A previous history of oophorectomy Environment 672-D001943 16234515 723 736 breast cancer Disease D001943 16234515 753 758 BRCA1 Gene 672 16234515 817 822 BRCA2 Gene 675 16234515 901 945 the oophorectomy was performed before age 40 Environment 672-D001943 16234515 983 988 BRCA1 Gene 672 16234515 1090 1116 15 years post-oophorectomy Environment 675-D001943 16234515 1164 1176 Oophorectomy Environment 672-D001943 16234515 1223 1236 breast cancer Disease D001943 16234515 1252 1257 BRCA1 Gene 672 16234515 1286 1298 oophorectomy Environment 675-D001943 16234515 1316 1321 BRCA2 Gene 675 17311260|t|Genetic polymorphisms in the one-carbon metabolism pathway and breast cancer risk: a population-based case-control study and meta-analyses. 17311260|t|Epidemiological evidence suggests that intake of folate and other B-vitamins and genetic variants in the one-carbon metabolism pathway could influence the risk of breast cancer. Previous studies have focused on 2 polymorphisms in the methylenetetrahydrofolate gene (MTHFR A222V and E429A); however, findings are inconclusive. In a large population-based case-control study in Poland (2,386 cases, 2,502 controls), we investigated the association between breast cancer risk and 13 polymorphisms in 6 one-carbon metabolism genes (MTHFR, MTR, MTRR, CBS, SHMT1 and SLC19A1). Data suggested an association between a nonsynonymous change in the gene coding for methionine synthase (MTR D919G) and reduced breast cancer risk: OR (95% CI) = 0.84 (0.73-0.96) and 0.85 (0.62-1.15) for heterozygous and homozygote variant genotypes, respectively, compared with common homozygotes; p-trend = 0.01, false discovery rate = 0.14. We found no significant associations between other variants and breast cancer risk, including MTHFR A222V or E429A. Meta-analyses including published studies of MTHFR A222V (8,330 cases and 10,825 controls) and E429A (6,521 cases and 8,515 controls) supported the lack of an overall association; however, studies suggested an increase in risk among premenopausal women. In conclusion, this report does not support a substantial overall association between the evaluated polymorphisms in the one-carbon metabolism pathway and breast cancer risk. 17311260 63 76 breast cancer Disease D001943 17311260 163 176 breast cancer Disease D001943 17311260 266 271 MTHFR Gene 4524 17311260 454 467 breast cancer Disease D001943 17311260 528 533 MTHFR Gene 4524 17311260 540 544 MTRR Gene 4552 17311260 551 556 SHMT1 Gene 6470 17311260 561 568 SLC19A1 Gene 6573 17311260 699 712 breast cancer Disease D001943 17311260 979 992 breast cancer Disease D001943 17311260 1009 1014 MTHFR Gene 4524 17311260 1076 1081 MTHFR Gene 4524 17311260 1264 1283 premenopausal women Environment 4524-D001943 17311260 1440 1453 breast cancer Disease D001943 21705483|t|Multi-institutional prostate cancer study of genetic susceptibility in populations of African descent. 21705483|t|Prostate cancer disparities have been reported in men of African descent who show the highest incidence, mortality, compared with other ethnic groups. Few studies have explored the genetic and environmental factors for prostate cancer in men of African ancestry. The glutathione-S-transferases family conjugates carcinogens before their excretion and is expressed in prostate tissue. This study addressed the role of GSTM1 and GSTT1 deletions on prostate cancer risk in populations of African descent. This multi-institutional case-control study gathered data from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database, the African-Caribbean Cancer Consortium (AC3) and Men of African Descent and Carcinoma of the Prostate Consortium (MADCaP). The analysis included 10 studies (1715 cases and 2363 controls), five in African-Americans, three in African-Caribbean and two in African men. Both the GSTM1 and the GSTT1 deletions showed significant inverse associations with prostate cancer [odds ratio (OR): 0.90, 95% confidence interval (CI) 0.83-0.97 and OR 0.88, 95% CI: 0.82-0.96, respectively]. The association was restricted to Caribbean and African populations. A significant positive association was observed between GSTM1 deletion and prostate cancer in smokers in African-American studies (OR: 1.28, 95% CI: 1.01-1.56), whereas a reduced risk was observed in never-smokers (OR: 0.66, 95% CI: 0.46-0.95). The risk of prostate cancer increased across quartiles of pack-years among subjects carrying the deletion of GSTM1 but not among subjects carrying a functional GSTM1. Gene-environment interaction between smoking and GSTM1 may be involved in the etiology of prostate cancer in populations of African descent. 21705483 20 35 prostate cancer Disease D011471 21705483 45 67 genetic susceptibility Disease D020022 21705483 0 15 Prostate cancer Disease D011471 21705483 219 234 prostate cancer Disease D011471 21705483 417 422 GSTM1 Gene 2944 21705483 427 432 GSTT1 Gene 2952 21705483 446 461 prostate cancer Disease D011471 21705483 569 591 Genetic Susceptibility Disease D020022 21705483 660 666 Cancer Disease D009369 21705483 679 682 AC3 Gene 109 21705483 715 724 Carcinoma Disease D002277 21705483 914 919 GSTM1 Gene 2944 21705483 928 933 GSTT1 Gene 2952 21705483 989 1004 prostate cancer Disease D011471 21705483 1240 1245 GSTM1 Gene 2944 21705483 1259 1274 prostate cancer Disease D011471 21705483 1278 1285 smokers Environment 2944-D011471 21705483 1384 1397 never-smokers Environment 2944-D011471 21705483 1441 1456 prostate cancer Disease D011471 21705483 1487 1497 pack-years Environment 2944-D011471 21705483 1538 1543 GSTM1 Gene 2944 21705483 1589 1594 GSTM1 Gene 2944 21705483 1633 1640 smoking Environment 2944-D011471 21705483 1645 1650 GSTM1 Gene 2944 21705483 1686 1701 prostate cancer Disease D011471 18990748|t|International Lung Cancer Consortium: pooled analysis of sequence variants in DNA repair and cell cycle pathways. 18990748|t|BACKGROUND: The International Lung Cancer Consortium was established in 2004. To clarify the role of DNA repair genes in lung cancer susceptibility, we conducted a pooled analysis of genetic variants in DNA repair pathways, whose associations have been investigated by at least 3 individual studies. METHODS: Data from 14 studies were pooled for 18 sequence variants in 12 DNA repair genes, including APEX1, OGG1, XRCC1, XRCC2, XRCC3, ERCC1, XPD, XPF, XPG, XPA, MGMT, and TP53. The total number of subjects included in the analysis for each variant ranged from 2,073 to 13,955 subjects. RESULTS: Four of the variants were found to be weakly associated with lung cancer risk with borderline significance: these were XRCC3 T241M [heterozygote odds ratio (OR), 0.89; 95% confidence interval (95% CI), 0.79-0.99 and homozygote OR, 0.84; 95% CI, 0.71-1.00] based on 3,467 cases and 5,021 controls from 8 studies, XPD K751Q (heterozygote OR, 0.99; 95% CI, 0.89-1.10 and homozygote OR, 1.19; 95% CI, 1.02-1.39) based on 6,463 cases and 6,603 controls from 9 studies, and TP53 R72P (heterozygote OR, 1.14; 95% CI, 1.00-1.29 and homozygote OR, 1.20; 95% CI, 1.02-1.42) based on 3,610 cases and 5,293 controls from 6 studies. OGG1 S326C homozygote was suggested to be associated with lung cancer risk in Caucasians (homozygote OR, 1.34; 95% CI, 1.01-1.79) based on 2,569 cases and 4,178 controls from 4 studies but not in Asians. The other 14 variants did not exhibit main effects on lung cancer risk. DISCUSSION: In addition to data pooling, future priorities of International Lung Cancer Consortium include coordinated genotyping and multistage validation for ongoing genome-wide association studies. 18990748 121 132 lung cancer Disease D008175 18990748 401 406 APEX1 Gene 328 18990748 408 412 OGG1 Gene 4968 18990748 414 419 XRCC1 Gene 7515 18990748 421 426 XRCC2 Gene 7516 18990748 428 433 XRCC3 Gene 7517 18990748 435 440 ERCC1 Gene 2067 18990748 442 445 XPD Gene 2068 18990748 447 450 XPF Gene 2072 18990748 452 455 XPG Gene 2073 18990748 457 460 XPA Gene 7507 18990748 462 466 MGMT Gene 4255 18990748 472 476 TP53 Gene 7157 18990748 657 668 lung cancer Disease D008175 18990748 715 720 XRCC3 Gene 7517 18990748 908 911 XPD Gene 2068 18990748 1064 1068 TP53 Gene 7157 18990748 1216 1220 OGG1 Gene 4968 18990748 1274 1285 lung cancer Disease D008175 18990748 1294 1304 Caucasians Environment 4968-D008175 18990748 1474 1485 lung cancer Disease D008175 12692111|t|Polymorphisms in the DNA repair genes XRCC1 and ERCC2, smoking, and lung cancer risk. 12692111|t|XRCC1 (X-ray cross-complementing group 1) and ERCC2 (excision repair cross-complementing group 2) are two major DNA repair proteins. Polymorphisms of these two genes have been associated with altered DNA repair capacity and cancer risk. We have described statistically significant interactions between the ERCC2 polymorphisms (Asp312Asn and Lys751Gln) and smoking in lung cancer risk. In this case-control study of 1091 Caucasian lung cancer patients and 1240 controls, we explored the gene-environment interactions between the XRCC1 Arg399Gln polymorphism, alone or in combination with the two ERCC2 polymorphisms, and cumulative smoking exposure in the development of lung cancer. The results were analyzed using logistic regression models, adjusting for relevant covariates. Overall, the adjusted odds ratio (OR) of XRCC1 Arg399Gln polymorphism (Gln/Gln versus Arg/Arg) was 1.3 [95% confidence interval (CI), 1.0-1.8]. Stratified analyses revealed that the ORs decreased as pack-years increased. For nonsmokers, the adjusted OR was 2.4 (95% CI, 1.2-5.0), whereas for heavy smokers (>/=55 pack-years), the OR decreased to 0.5 (95% CI, 0.3-1.0). When the three polymorphisms were evaluated together, the adjusted ORs of the extreme genotype combinations of variant alleles (individuals with 5 or 6 variant alleles) versus wild genotype (individuals with 0 variant alleles) were 5.2 (95% CI, 1.7-16.6) for nonsmokers and 0.3 (95% CI, 0.1-0.8) for heavy smokers, respectively. Similar gene-smoking interaction associations were found when pack-years of smoking (or smoking duration and smoking intensity) was fitted as a continuous variable. In conclusion, cumulative cigarette smoking plays an important role in altering the direction and magnitude of the associations between the XRCC1 and ERCC2 polymorphisms and lung cancer risk. 12692111 38 43 XRCC1 Gene 7515 12692111 48 53 ERCC2 Gene 2068 12692111 68 79 lung cancer Disease D008175 12692111 0 5 XRCC1 Gene 7515 12692111 7 40 X-ray cross-complementing group 1 Gene 7515 12692111 46 51 ERCC2 Gene 2068 12692111 53 96 excision repair cross-complementing group 2 Gene 2068 12692111 224 230 cancer Disease D009369 12692111 306 311 ERCC2 Gene 2068 12692111 367 378 lung cancer Disease D008175 12692111 430 441 lung cancer Disease D008175 12692111 528 533 XRCC1 Gene 7515 12692111 595 600 ERCC2 Gene 2068 12692111 670 681 lung cancer Disease D008175 12692111 819 824 XRCC1 Gene 7515 12692111 977 997 pack-years increased Environment 7515-D008175 12692111 1070 1083 heavy smokers Environment 7515-D008175 12692111 1085 1101 >/=55 pack-years Environment 7515-D008175 12692111 1447 1460 heavy smokers Environment 7515-D008175 12692111 1447 1460 heavy smokers Environment 2068-D008175 12692111 1538 1559 pack-years of smoking Environment 7515-D008175 12692111 1538 1559 pack-years of smoking Environment 2068-D008175 12692111 1564 1580 smoking duration Environment 7515-D008175 12692111 1564 1580 smoking duration Environment 2068-D008175 12692111 1585 1602 smoking intensity Environment 7515-D008175 12692111 1585 1602 smoking intensity Environment 2068-D008175 12692111 1656 1684 cumulative cigarette smoking Environment 7515-D008175 12692111 1656 1684 cumulative cigarette smoking Environment 2068-D008175 12692111 1781 1786 XRCC1 Gene 7515 12692111 1791 1796 ERCC2 Gene 2068 12692111 1815 1826 lung cancer Disease D008175 20949557|t|Genetic variation in C-reactive protein in relation to colon and rectal cancer risk and survival. 20949557|t|C-reactive protein (CRP), a biomarker of inflammation, has been shown to be influenced by genetic variation in the CRP gene. In this study, we test the hypothesis that genetic variation in CRP influences both the risk of developing colon and rectal cancer and survival. Two population-based studies of colon cancer (n = 1,574 cases, 1,970 controls) and rectal (n = 791 cases, 999 controls) were conducted. We evaluated four CRP tagSNPs: rs1205 (G > A, 3' UTR); rs1417938 (T > A, intron); rs1800947 (G > C, L184L); and rs3093075 (C > A, 3' flanking). The CRP rs1205 AA genotype was associated with an increased risk of colon cancer (OR 1.3, 95%CI 1.1-1.7), whereas the rs3093075 A allele was associated with a reduced risk of rectal cancer (OR 0.7, 95%CI 0.5-0.9). The strongest association for the rs1205 polymorphism and colon cancer was observed among those with KRAS2 mutations (OR 1.5, 95%CI 1.1-2.0). The CRP rs1205 AA genotype also was associated with an increased risk of CIMP+ rectal tumors (OR 2.5, 95%CI 1.2-5.3); conversely, the rs1417938 A allele was associated with a reduced risk of CIMP+ rectal tumors (OR 0.5, 95%CI 0.3-0.9). We observed interactions between CRP rs1800947 and BMI and family history of CRC in modifying risk of both colon and rectal cancer. These data suggest that genetic variation in the CRP gene influences risk of both colon and rectal cancer development. 20949557 21 39 C-reactive protein Gene 1401 20949557 65 78 rectal cancer Disease D012004 20949557 0 18 C-reactive protein Gene 1401 20949557 20 23 CRP Gene 1401 20949557 41 53 inflammation Disease D007249 20949557 115 118 CRP Gene 1401 20949557 189 192 CRP Gene 1401 20949557 242 255 rectal cancer Disease D012004 20949557 302 314 colon cancer Disease D003110 20949557 424 427 CRP Gene 1401 20949557 554 557 CRP Gene 1401 20949557 618 630 colon cancer Disease D003110 20949557 725 738 rectal cancer Disease D012004 20949557 822 834 colon cancer Disease D003110 20949557 865 870 KRAS2 Gene 3845 20949557 910 913 CRP Gene 1401 20949557 985 998 rectal tumors Disease D012004 20949557 1103 1116 rectal tumors Disease D012004 20949557 1175 1178 CRP Gene 1401 20949557 1193 1196 BMI Environment 1401-D012004 20949557 1193 1196 BMI Environment 1401-D003110 20949557 1201 1222 family history of CRC Environment 1401-D012004 20949557 1201 1222 family history of CRC Environment 1401-D003110 20949557 1259 1272 rectal cancer Disease D012004 20949557 1323 1326 CRP Gene 1401 20949557 1366 1379 rectal cancer Disease D012004 17640440|t|COMT Val158Met moderation of stress-induced psychosis. 17640440|t|BACKGROUND: Exposure to stressful life events increases the risk of developing a psychotic disorder. Moreover, increased reactivity to stress seems to represent part of the vulnerability for psychosis. This study aimed to investigate whether a functional polymorphism in the catechol-O-methyltransferase (COMT Val(158)Met) gene moderates the psychosis-inducing effects of stress. METHOD: A semi-experimental stress exposure paradigm was used in a sample of 306 genotyped young men (aged 19-24 years), in whom measures of psychotic symptoms were obtained at recruitment in the Greek army (exposed condition) and again after 18 months of military training (unexposed condition). RESULTS: Stress exposure at army induction was associated with an increased level of psychotic symptoms. In addition, carriers of the COMT Val(158)Met Val allele were more susceptible to the effect of stress on the psychosis outcome than those with the Met/Met genotype (test for interaction: chi2 = 5.02, df = 1, p = 0.025). CONCLUSION: The COMT Val(158)Met genotype may moderate the effect of stress on psychotic symptoms. 17640440 0 4 COMT Gene 1312 17640440 29 35 stress Environment 1312-D011605 17640440 44 53 psychosis Disease D011605 17640440 81 99 psychotic disorder Disease D011618 17640440 191 200 psychosis Disease D011605 17640440 275 303 catechol-O-methyltransferase Gene 1312 17640440 305 309 COMT Gene 1312 17640440 342 351 psychosis Disease D011605 17640440 521 539 psychotic symptoms Disease D011605 17640440 762 780 psychotic symptoms Disease D011605 17640440 811 815 COMT Gene 1312 17640440 878 884 stress Environment 1312-D011605 17640440 892 901 psychosis Disease D011605 17640440 1019 1023 COMT Gene 1312 17640440 1072 1078 stress Environment 1312-D011605 17640440 1082 1100 psychotic symptoms Disease D011605 19582567|t|Impact of the interaction between the 5HTTLPR polymorphism and maltreatment on adolescent depression. A population-based study. 19582567|t|Serotonin plays a central role in mood regulation and the development of depressive disorders. The present study investigated whether a functional polymorphism (5HTTLPR) of the serotonin transporter gene interacts with maltreatment in the prediction of depression. A cohort of 17-18 years old students (n = 1,482) anonymously completed the Survey of Adolescent Life and Health in Vestmanland 2006 and gave a saliva sample for DNA extraction. An association between maltreatment and adolescent depression was found independent of sex. When the whole population was analyzed, no main effect of 5HTTLPR in association with depression was found. When separated by sex, a significant main effect and a G x E interaction effect of the SS allele was found among girls. No gene main effect or G x E interaction effect was found among boys. The present study confirms previous findings of sex differences in interaction effects between the 5HTTLPR polymorphism and maltreatment in the prediction of adolescent depression. 19582567 38 45 5HTTLPR Gene 6532 19582567 63 75 maltreatment Environment 6532-D003866 19582567 90 100 depression Disease D003866 19582567 73 93 depressive disorders Disease D003866 19582567 161 168 5HTTLPR Gene 6532 19582567 177 198 serotonin transporter Gene 6532 19582567 253 263 depression Disease D003866 19582567 493 503 depression Disease D003866 19582567 592 599 5HTTLPR Gene 6532 19582567 620 630 depression Disease D003866 19582567 931 938 5HTTLPR Gene 6532 19582567 956 968 maltreatment Environment 6532-D003866 19582567 1001 1011 depression Disease D003866 17675654|t|Joint effects of the N-acetyltransferase 1 and 2 (NAT1 and NAT2) genes and smoking on bladder carcinogenesis: a literature-based systematic HuGE review and evidence synthesis. 17675654|t|Bladder cancer is an increasingly important international public health problem, with over 330,000 new cases being diagnosed each year worldwide. In a systematic review and evidence synthesis, the authors investigated the joint effects of the N-acetyltransferase genes NAT1 and NAT2 and cigarette smoking on bladder carcinogenesis. Studies were identified through an exhaustive search of multiple electronic databases and reference lists and through direct contact with study authors and experts. Random-effects meta-analysis was used within a Bayesian framework to investigate individual effects of NAT1 and NAT2 acetylation status on bladder cancer risk, while a novel approach was used to investigate joint effects of these two genes with cigarette smoking. An increased risk of bladder cancer was found in NAT2 slow acetylators (odds ratio = 1.46, 95% credible interval (CI): 1.26, 1.68) but not in NAT1 fast acetylators (odds ratio = 1.01, 95% CI: 0.86, 1.22). The joint effects in the highest risk category (NAT2 slow acetylator, NAT1 fast acetylator, and current or ever cigarette smoking) as compared with the reference category (NAT2 fast acetylator, NAT1 slow acetylator, and never smoking) were associated with an odds ratio of 2.73 (95% CI: 1.70, 4.31). The importance of considering joint effects between genetic and environmental factors in the etiology of common complex diseases is underlined. 17675654 21 48 N-acetyltransferase 1 and 2 Gene 10 17675654 50 54 NAT1 Gene 9 17675654 59 63 NAT2 Gene 10 17675654 75 82 smoking Environment 10-D001749 17675654 75 82 smoking Environment 9-D001749 17675654 94 108 carcinogenesis Disease D063646 17675654 0 14 Bladder cancer Disease D001749 17675654 269 273 NAT1 Gene 9 17675654 278 282 NAT2 Gene 10 17675654 316 330 carcinogenesis Disease D063646 17675654 600 604 NAT1 Gene 9 17675654 609 613 NAT2 Gene 10 17675654 636 650 bladder cancer Disease D001749 17675654 782 796 bladder cancer Disease D001749 17675654 810 814 NAT2 Gene 10 17675654 903 907 NAT1 Gene 9 17675654 1014 1018 NAT2 Gene 10 17675654 1036 1040 NAT1 Gene 9 17675654 1062 1095 current or ever cigarette smoking Environment 10-D001749 17675654 1062 1095 current or ever cigarette smoking Environment 9-D001749 17675654 1138 1142 NAT2 Gene 10 17675654 1160 1164 NAT1 Gene 9 17675654 1378 1394 complex diseases Disease 1 15111762|t|Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 (UGT1A1) and risk of breast cancer. 15111762|t|Uridine diphospho-glucuronosyltransferase 1A1 (UGT1A1) is involved in catalyzing estrogen, the hormone that plays a central role in the etiology of breast cancer. A common polymorphism [A(TA)6TAA (allele *1) to A(TA)7TAA change (allele *28)] in the TATA-box of the promoter region of the UGT1A1 gene has been reported to be associated with a reduced transcription of this gene. We investigated the association of this polymorphism with the risk of breast cancer among 1047 breast cancer cases and 1083 community controls in the Shanghai Breast Cancer Study, a population-based case-control study. Approximately same proportion of cases (12.5%) and controls (13.0%) carried the variant allele *28 in the Chinese population (p = 0.32). When stratified by age, carrying the *28 allele was associated with an increased risk of breast cancer among women aged less than 40 years (odds ratio [OR] = 1.7; 95% CI = 1.0-2.7) but not among women 40 years old and over (OR = 0.8; 0.7-1.1). Only a few women were homozygous for the *28 allele, precluding a detailed gene-dose association analysis. Additional analyses showed that, the elevated risk associated with the UGT1A1 *28 allele among young women was primarily seen in women who had a later menarche, short menstrual years, absence of family history of breast cancer, low waist-to-hip ratio, or low body-mass index. These results suggested that the *28 allele in the UGT1A1 gene may be associated with an increased risk for breast cancer among Chinese women under age 40. No significant associations were observed with *28 allele and breast cancer risk by estrogen receptor/progesterone receptor status. 15111762 25 70 uridine diphospho-glucuronosyltransferase 1A1 Gene 54658 15111762 72 78 UGT1A1 Gene 54658 15111762 92 105 breast cancer Disease D001943 15111762 0 45 Uridine diphospho-glucuronosyltransferase 1A1 Gene 54658 15111762 47 53 UGT1A1 Gene 54658 15111762 148 161 breast cancer Disease D001943 15111762 288 294 UGT1A1 Gene 54658 15111762 448 461 breast cancer Disease D001943 15111762 473 486 breast cancer Disease D001943 15111762 823 836 breast cancer Disease D001943 15111762 843 872 women aged less than 40 years Environment 54658-D001943 15111762 1156 1162 UGT1A1 Gene 54658 15111762 1228 1244 a later menarche Environment 54658-D001943 15111762 1246 1267 short menstrual years Environment 54658-D001943 15111762 1269 1311 absence of family history of breast cancer Environment 54658-D001943 15111762 1298 1311 breast cancer Disease D001943 15111762 1313 1335 low waist-to-hip ratio Environment 54658-D001943 15111762 1340 1359 low body-mass index Environment 54658-D001943 15111762 1412 1418 UGT1A1 Gene 54658 15111762 1469 1482 breast cancer Disease D001943 15111762 1489 1515 Chinese women under age 40 Environment 54658-D001943 15111762 1579 1592 breast cancer Disease D001943 21771723|t|Novel genetic variants in the chromosome 5p15.33 region associate with lung cancer risk. 21771723|t|Chromosome 5p15.33 has been identified by genome-wide association studies as one of the regions that associate with lung cancer risk. A few single-nucleotide polymorphisms (SNPs) in the telomerase reverse transcriptase (TERT) and cleft lip and palate transmembrane 1-like (CLPTM1L) genes located in this region have shown consistent associations. We performed dense genotyping of SNPs in this region to refine the previously reported association signals for lung cancer risk. Two hundred and fifteen SNPs were genotyped on an Illumina iSelect panel, in a hospital-based case-control study of 1681 lung cancer cases and 1235 unaffected controls. Association was tested using unconditional logistic regression, while adjusting for age, sex and pack-years smoked. Furthermore, since many of the SNPs were in linkage disequilibrium (LD), haplotype blocks were constructed, from which tagging SNPs at an r(2) threshold of >/=0.95 were included in a stepwise forward selection logistic regression model. Of the 215 SNPs, 69 were significant at P < 0.05 in univariate analysis; of these, 35 SNPs meeting the r(2) threshold were included in the multiple logistic regression model. Two SNPs, rs370348 (odds ratio = 0.76, P = 1.6 x 10(-6)) and rs4975538 (odds ratio = 1.18, P = 0.005), significantly associated with risk in the overall sample. Among ever smokers, rs4975615 (odds ratio = 0.75, P = 1.2 x 10(-4)) and rs4975538 (odds ratio = 1.26, P = 0.002) were significant, whereas among never-smokers, rs451360 (odds ratio = 0.62, P = 7.6 x 10(-5)) was significant. We refined the consistent association signal in this region, allowing for the considerable LD between SNPs and identified four novel SNPs that were independently and significantly associated with lung cancer risk. Results of these analyses strongly suggest effects on risk from several loci in the TERT/CLPTM1L region. 21771723 71 82 lung cancer Disease D008175 21771723 116 127 lung cancer Disease D008175 21771723 186 218 telomerase reverse transcriptase Gene 7015 21771723 220 224 TERT Gene 7015 21771723 230 239 cleft lip Disease D002971 21771723 273 280 CLPTM1L Gene 81037 21771723 458 469 lung cancer Disease D008175 21771723 597 608 lung cancer Disease D008175 21771723 1340 1352 ever smokers Environment 7015-D008175 21771723 1340 1352 ever smokers Environment 81037-D008175 21771723 1479 1492 never-smokers Environment 7015-D008175 21771723 1479 1492 never-smokers Environment 81037-D008175 21771723 1754 1765 lung cancer Disease D008175 21771723 1856 1860 TERT Gene 7015 21771723 1861 1868 CLPTM1L Gene 81037 17389614|t|Folate-related genes and the risk of tobacco-related cancers in Central Europe. 17389614|t|Folate has been hypothesized to protect against aero-digestive cancers although the evidence is not yet conclusive due to possible confounding by other dietary factors. Sequence variants in folate pathway were suggested to be associated with plasma folate levels and are unlikely to be confounded by other lifestyle factors. We therefore investigated the effects of key folate genetic variants on the risk of aero-digestive cancers and their potential effect modification by folate intake in a multicenter study in Central Europe. A total of 2250 lung cases, 811 upper aero-digestive tract cases and 2899 controls were recruited with blood samples. The methylenetetrahydrofolate reductase (MTHFR) C677T variant was associated with an increased risk of lung cancer with an odds ratio (OR) for homozygote variant of 1.37 [95% confidence interval (CI) = 1.10-1.71]. The two MTHFR variants were in strong linkage disequilibrium, and 677T-1298A appeared to be the primary haplotype associated with cancer risk. The risk estimates for MTHFR 677T/677T genotype was more prominent among lung cancer patients with young onset (OR = 1.92, 95% CI = 1.12-3.29). When stratified by dietary intake of folate, the effect of the MTHFR 677T variant was more prominent among subjects with low intake of folate: the ORs for 677T/677T genotype among subjects with the lowest decile were 2.60 (95% CI = 1.39-4.88) and 4.14 (95% CI = 1.47-11.7) for lung and upper aero-digestive tract cancer, respectively. In conclusion, we identified a moderate effect of MTHFR C677T on lung cancer risk and a possible effect modification by folate intake that is consistent with the functional data. These results support an important role of folate in protecting against tobacco-related cancers. 17389614 53 60 cancers Disease D009369 17389614 63 70 cancers Disease D009369 17389614 424 431 cancers Disease D009369 17389614 653 688 methylenetetrahydrofolate reductase Gene 4524 17389614 690 695 MTHFR Gene 4524 17389614 752 763 lung cancer Disease D008175 17389614 871 876 MTHFR Gene 4524 17389614 993 999 cancer Disease D009369 17389614 1029 1034 MTHFR Gene 4524 17389614 1079 1090 lung cancer Disease D008175 17389614 1213 1218 MTHFR Gene 4524 17389614 1271 1291 low intake of folate Environment 4524-D008175 17389614 1463 1469 cancer Disease D009369 17389614 1535 1540 MTHFR Gene 4524 17389614 1550 1561 lung cancer Disease D008175 17389614 1605 1618 folate intake Environment 4524-D008175 17389614 1752 1759 cancers Disease D009369 22189957|t|Functional genetic variants of c-Jun and their interaction with smoking and drinking increase the susceptibility to lung cancer in southern and eastern Chinese. 22189957|t|Human proto-oncogene c-Jun and c-Fos assemble the activator protein-1 complex which is a crucial transcription factor responding to environmental factors and promotes tumorgenesis. We hypothesized that genetic variants in these two genes may alter the carriers' susceptibility to lung cancer. In two independent case-control studies, we genotyped three putative functional polymorphisms (-1318T>G and -673T>C of c-Jun; -60C>T of c-Fos) in southern Chinese and then validated the association in eastern Chinese. We found that compared to -1318TT genotype, the -1318GT/GG variant genotypes had an increased lung cancer risk (OR=1.46, 95% CI=1.26-1.69), and the -673CC genotype had an increased lung cancer risk compared to -673TT/CT genotypes (OR=1.35, 95% CI=1.17-1.56) in the total 1,559 cases versus 1,679 controls. After combining these two loci, the number of the risk genotypes was associated with increased cancer risk in a dose-response manner (ptrend=2.21x10(-11)); moreover, the risk genotypes interacted with smoking or drinking status on increasing cancer risk (p values of interaction were 0.009 and 0.007, respectively). Further, we found that those with -1318GT/GG genotypes, -673CC genotypes or both genotypes in c-Jun had higher mRNA and protein expression levels in vivo, and those variants had higher transcription activities in reporter genes in vitro, especially under the stimuli with tobacco extract or alcohol mixture as luciferase assay shown. However, for -60C>T of c-Fos, no significant association was observed for lung cancer risk. Our data suggested that the genetic variants in c-Jun (-1318T>G and -673T>C) increase the carriers' susceptibility to lung cancer via interaction with smoking or drinking on increasing the c-Jun's expression. 22189957 31 36 c-Jun Gene 3725 22189957 64 71 smoking Environment 3725-D008175 22189957 76 84 drinking Environment 3725-D008175 22189957 116 127 lung cancer Disease D008175 22189957 6 26 proto-oncogene c-Jun Gene 3725 22189957 31 36 c-Fos Gene 2353 22189957 50 69 activator protein-1 Gene 3725 22189957 280 291 lung cancer Disease D008175 22189957 412 417 c-Jun Gene 3725 22189957 429 434 c-Fos Gene 2353 22189957 605 616 lung cancer Disease D008175 22189957 692 703 lung cancer Disease D008175 22189957 912 918 cancer Disease D009369 22189957 1018 1025 smoking Environment 3725-D008175 22189957 1029 1044 drinking status Environment 3725-D008175 22189957 1059 1065 cancer Disease D009369 22189957 1227 1232 c-Jun Gene 3725 22189957 1405 1420 tobacco extract Environment 3725-D008175 22189957 1424 1439 alcohol mixture Environment 3725-D008175 22189957 1490 1495 c-Fos Gene 2353 22189957 1541 1552 lung cancer Disease D008175 22189957 1607 1612 c-Jun Gene 3725 22189957 1677 1688 lung cancer Disease D008175 22189957 1710 1717 smoking Environment 3725-D008175 22189957 1721 1729 drinking Environment 3725-D008175 22189957 1748 1753 c-Jun Gene 3725 18523027|t|Mismatch repair polymorphisms and risk of colon cancer, tumour microsatellite instability and interactions with lifestyle factors. 18523027|t|BACKGROUND: Germline mutations in DNA mismatch repair (MMR) genes cause Lynch syndrome colon cancers. Less understood is the risk of colon cancer associated with common polymorphisms in MMR genes and the potential interacting role of lifestyle factors known to damage DNA. METHODS: A study was conducted to examine whether MLH1 (-93G>A and Ile219Val) and MSH6 (Gly39Glu) polymorphisms were associated with risk of colon cancer in data from 1609 colon cancer cases and 1972 controls. Genotype data were further stratified by microsatellite instability status, smoking, alcohol, Western diet, alcohol and obesity, to investigate potential heterogeneity. RESULTS: The MSH6 39Glu allele was associated with increased risk of colon cancer among men (Gly/Glu or Glu/Glu vs Gly/Gly, OR 1.27; 95% CI 1.04 to 1.54). Neither MLH1 polymorphism was associated with colon cancer risk overall. When stratified by microsatellite stability status, however, the MLH1 -93A allele was associated with a more than doubling in microsatellite instability (MSI)-positive colon cancer risk (AA vs GG, OR 2.47; 95% CI 1.48 to 4.11); no associations were observed between the MMR polymorphisms examined and MSI-negative colon cancer. Statistically significant interactions were observed between: MLH1 -93G>A and smoking (MSI-negative colon cancer only, p value interaction: 0.005); and MLH1 Ile219Val and Western diet (p value interaction: 0.03). CONCLUSIONS: The MSH6 Gly39Glu and MLH1 -93G>A polymorphisms were associated with risk of overall colon and MSI-positive colon cancers, respectively. Risk for colon cancer, stratified by MMR genotype, was further modified by smoking and Western diet. 18523027 42 54 colon cancer Disease D003110 18523027 56 89 tumour microsatellite instability Disease 1 18523027 72 100 Lynch syndrome colon cancers Disease 1 18523027 139 145 cancer Disease D009369 18523027 323 327 MLH1 Gene 4292 18523027 355 359 MSH6 Gene 2956 18523027 420 426 cancer Disease D009369 18523027 451 457 cancer Disease D009369 18523027 524 550 microsatellite instability Disease D053842 18523027 603 610 obesity Disease D009765 18523027 665 669 MSH6 Gene 2956 18523027 727 733 cancer Disease D009369 18523027 815 819 MLH1 Gene 4292 18523027 859 865 cancer Disease D009369 18523027 945 949 MLH1 Gene 4292 18523027 1006 1032 microsatellite instability Disease D053842 18523027 1006 1047 microsatellite instability (MSI)-positive Environment 4292-D003110 18523027 1034 1037 MSI Disease D053842 18523027 1054 1060 cancer Disease D009369 18523027 1181 1184 MSI Disease D053842 18523027 1200 1206 cancer Disease D009369 18523027 1270 1274 MLH1 Gene 4292 18523027 1286 1293 smoking Environment 4292-D003110 18523027 1295 1298 MSI Disease D053842 18523027 1314 1320 cancer Disease D009369 18523027 1360 1364 MLH1 Gene 4292 18523027 1379 1391 Western diet Environment 4292-D003110 18523027 1438 1442 MSH6 Gene 2956 18523027 1456 1460 MLH1 Gene 4292 18523027 1529 1532 MSI Disease D053842 18523027 1542 1555 colon cancers Disease D003110 18523027 1586 1592 cancer Disease D009369 18523027 1646 1653 smoking Environment 4292-D003110 18523027 1658 1670 Western diet Environment 4292-D003110 16489531|t|PPARgamma and colon and rectal cancer: associations with specific tumor mutations, aspirin, ibuprofen and insulin-related genes (United States). 16489531|t|We hypothesize that the peroxisome proliferator-activated receptor-gamma (PPARgamma) is associated with colorectal cancer given its association with insulin, diabetes, obesity, and inflammation. In this study, we evaluated the association between colorectal cancer and specific tumor mutations and the Pro12Ala (P12A) PPARgamma polymorphism. We also evaluated interactions between the PPARgamma gene and other insulin-related genes and use of aspirin and non-steroidal anti-inflammatory drug use. Data were available from 1,577 cases of colon cancer that were matched to 1,971 population-based controls and 794 cases of rectal cancer that were matched to 1,001 population-based controls. Colon tumors from the case subjects were evaluated for p53 and Ki-ras mutations and microsatellite instability (MSI). Insulin-related genes evaluated were the Bsm1, polyA, and Fok1 polymorphisms of the VDR gene; the G972R IRS1 polymorphism; the G1057D IRS2 polymorphism; the 19CA repeat polymorphism of the IGF1 gene; and the -200A>C IGFBP3 polymorphism. The odds ratio (OR) between the PA/AA genotypes and proximal tumors was 0.83 (95% CI: 0.69-1.01); for distal tumors was 1.00 (95% CI: 0.83-1.21); and for rectal tumors was 1.04 (95% CI: 0.86-1.25). Evaluation of specific types of tumor mutations showed that colon cancer cases with the PA or AA genotypes were less likely to have p53 tumor mutations (OR 0.78; 95% CI: 0.62-0.99), specifically transition mutations (OR 0.74; 95% CI: 0.56-0.97). Colon cancer cases also were less likely to have a tumor with MSI if they had the PA or AA PPARgamma genotype (OR 0.68; 95% CI: 0.47-0.98); differences in Ki-ras mutations were not seen in colon tumors by PPARgamma genotype. Those who did not take ibuprofen-type drugs and had the PA or AA genotypes were at a significantly greater risk of rectal cancer (OR 2.11; 95% CI: 1.52-2.92; p interaction 0.03) than people with the PP genotype regardless of ibuprofen-type drug use. There was a significant interaction between the -200A>C IGFBP3 polymorphism and the Pro12Ala PPARgamma polymorphism and risk of colon cancer (p for interaction = 0.02) with individuals being at significantly lower risk if they had both the CC IGFBP3 genotype and the PA/AA PPARgamma genotype. For rectal cancer there was a significant interaction between the Bsm1/polyA polymorphisms (p = 0.001) of the VDR gene and the PA/AA Pro12Ala PPARgamma polymorphism with the highest risk group being those with both the PA/AA Pro12Ala PPARgamma and the BB/SS VDR genotypes. These data suggest that PPARgamma may be associated with many aspects of colorectal cancer including insulin- and inflammation-related mechanisms. 16489531 0 9 PPARgamma Gene 5468 16489531 24 37 rectal cancer Disease D012004 16489531 66 71 tumor Disease D009369 16489531 24 72 peroxisome proliferator-activated receptor-gamma Gene 5468 16489531 74 83 PPARgamma Gene 5468 16489531 104 121 colorectal cancer Disease D015179 16489531 158 166 diabetes Disease D003920 16489531 168 175 obesity Disease D009765 16489531 181 193 inflammation Disease D007249 16489531 247 264 colorectal cancer Disease D015179 16489531 278 283 tumor Disease D009369 16489531 318 327 PPARgamma Gene 5468 16489531 385 394 PPARgamma Gene 5468 16489531 537 549 colon cancer Disease D003110 16489531 627 633 cancer Disease D009369 16489531 694 700 tumors Disease D009369 16489531 743 746 p53 Gene 7157 16489531 751 757 Ki-ras Gene 3845 16489531 772 798 microsatellite instability Disease D053842 16489531 800 803 MSI Disease D053842 16489531 890 893 VDR Gene 7421 16489531 910 914 IRS1 Gene 3667 16489531 940 944 IRS2 Gene 8660 16489531 995 999 IGF1 Gene 3479 16489531 1022 1028 IGFBP3 Gene 3486 16489531 1104 1110 tumors Disease D009369 16489531 1152 1158 tumors Disease D009369 16489531 1197 1210 rectal tumors Disease D012004 16489531 1273 1278 tumor Disease D009369 16489531 1301 1313 colon cancer Disease D003110 16489531 1373 1376 p53 Gene 7157 16489531 1377 1382 tumor Disease D009369 16489531 1487 1499 Colon cancer Disease D003110 16489531 1538 1543 tumor Disease D009369 16489531 1549 1552 MSI Disease D053842 16489531 1578 1587 PPARgamma Gene 5468 16489531 1642 1648 Ki-ras Gene 3845 16489531 1682 1688 tumors Disease D009369 16489531 1692 1701 PPARgamma Gene 5468 16489531 1712 1755 Those who did not take ibuprofen-type drugs Environment 5468-D012004 16489531 1834 1840 cancer Disease D009369 16489531 2018 2024 IGFBP3 Gene 3486 16489531 2055 2064 PPARgamma Gene 5468 16489531 2090 2102 colon cancer Disease D003110 16489531 2205 2211 IGFBP3 Gene 3486 16489531 2235 2244 PPARgamma Gene 5468 16489531 2266 2272 cancer Disease D009369 16489531 2365 2368 VDR Gene 7421 16489531 2397 2406 PPARgamma Gene 5468 16489531 2489 2498 PPARgamma Gene 5468 16489531 2513 2516 VDR Gene 7421 16489531 2552 2561 PPARgamma Gene 5468 16489531 2601 2618 colorectal cancer Disease D015179 16489531 2642 2654 inflammation Disease D007249 23090633|t|The interaction between smoking and GSTM1 variant on lung cancer in the Chinese population. 23090633|t|Smoking and the deletion of GSTM1 variant are two risk factors of lung cancer. This meta-analysis was performed to examine the GSTM1-smoking interaction on lung cancer in the Chinese population. PubMed, Web of Science, and other Chinese databases were searched to include all the related studies. The number of subjects with two GSTM1 genotypes across different smoking status was extracted. The pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated using fixed- or random-effect model. A total of 4,345 cases and 5,031 controls from 30 studies were included in the meta-analysis. Compared with nonsmokers having power GSTM1, the pooled ORs with 95 % CIs for lung cancer in smokers with power GSTM1, in nonsmokers with null GSTM1, and in smokers with null GSTM1 were 2.24 (1.82-2.76), 1.48 (1.23-1.79), and 4.18 (3.38-5.16), respectively. This meta-analysis showed that there was an interaction between the GSTM1 and smoking on the risk of lung cancer in the Chinese. Further studies are needed to examine the interactions between other environmental factors and GSTM1 on the risk of lung cancer. 23090633 24 31 smoking Environment 2944-D008175 23090633 36 41 GSTM1 Gene 2944 23090633 53 64 lung cancer Disease D008175 23090633 28 33 GSTM1 Gene 2944 23090633 66 77 lung cancer Disease D008175 23090633 127 132 GSTM1 Gene 2944 23090633 156 167 lung cancer Disease D008175 23090633 329 334 GSTM1 Gene 2944 23090633 643 648 GSTM1 Gene 2944 23090633 683 694 lung cancer Disease D008175 23090633 698 705 smokers Environment 2944-D008175 23090633 717 722 GSTM1 Gene 2944 23090633 748 753 GSTM1 Gene 2944 23090633 762 769 smokers Environment 2944-D008175 23090633 780 785 GSTM1 Gene 2944 23090633 931 936 GSTM1 Gene 2944 23090633 941 948 smoking Environment 2944-D008175 23090633 964 975 lung cancer Disease D008175 23090633 1087 1092 GSTM1 Gene 2944 23090633 1108 1119 lung cancer Disease D008175 22128864|t|Evidence that interactive effects of COMT and MTHFR moderate psychotic response to environmental stress. 22128864|t|OBJECTIVE: A functional interaction between Catechol-O-Methyltransferase (COMT) Val158Met and methylenetetrahydrofolate reductase (MTHFR) C677T has been shown to differentially affect cognition in patients with schizophrenia and healthy controls; the effect of COMT Val158Met x MTHFR interaction on resilience to stress in patients and controls remains to be examined. METHOD: A total of 98 patients with non-affective psychotic disorder and 118 controls were genotyped for MTHFR C677T, MTHFR A1298C, and COMTVal158Met. Daily life reactivity to stress, modelled as the effect of daily life stress on psychotic experiences, was measured using the experience sampling method (ESM). RESULTS: The MTHFR C677T genotype moderated the interaction between COMT Val158Met genotype and stress in patients (P < 0.0001), but not in controls (P = 0.68). Further examination of this interaction revealed that in patients with the MTHFR 677 T-allele, COMT Met/Met individuals displayed the largest increases in psychotic symptoms in reaction to ESM stress [chi(2)(2) = 29.51; P < 0.0001], whereas in patients with the MTHFR 677 C/C genotype no significant COMT Val158Met x ESM stress interaction was apparent [chi(2)(2) = 3.65; P = 0.16]. No moderating effect of MTHFR A1298C was found. CONCLUSION: Stress reactivity associated with COMT Val158Met in patients with psychosis may crucially depend on MTHFR C677T genotype. 22128864 37 41 COMT Gene 1312 22128864 46 51 MTHFR Gene 4524 22128864 61 70 psychotic Disease D011618 22128864 83 103 environmental stress Environment 4524-D011618 22128864 83 103 environmental stress Environment 1312-D011618 22128864 44 72 Catechol-O-Methyltransferase Gene 1312 22128864 74 78 COMT Gene 1312 22128864 94 129 methylenetetrahydrofolate reductase Gene 4524 22128864 131 136 MTHFR Gene 4524 22128864 211 224 schizophrenia Disease D012559 22128864 261 265 COMT Gene 1312 22128864 278 283 MTHFR Gene 4524 22128864 419 437 psychotic disorder Disease D011618 22128864 474 479 MTHFR Gene 4524 22128864 487 492 MTHFR Gene 4524 22128864 600 609 psychotic Disease D011618 22128864 693 698 MTHFR Gene 4524 22128864 748 752 COMT Gene 1312 22128864 776 782 stress Environment 4524-D011618 22128864 776 782 stress Environment 1312-D011618 22128864 916 921 MTHFR Gene 4524 22128864 936 940 COMT Gene 1312 22128864 996 1014 psychotic symptoms Disease D011605 22128864 1034 1040 stress Environment 4524-D011618 22128864 1034 1040 stress Environment 1312-D011618 22128864 1103 1108 MTHFR Gene 4524 22128864 1141 1145 COMT Gene 1312 22128864 1248 1253 MTHFR Gene 4524 22128864 1284 1301 Stress reactivity Environment 4524-D011618 22128864 1284 1301 Stress reactivity Environment 1312-D011618 22128864 1318 1322 COMT Gene 1312 22128864 1350 1359 psychosis Disease D011605 22128864 1384 1389 MTHFR Gene 4524 22351525|t|TERT's role in colorectal carcinogenesis. 22351525|t|Telomerase reverse transcriptase (TERT) is one of the main functional subunits of the telomerase enzyme, which functions to increase telomere length. Studies have suggested that TERT may be important to the etiology of colorectal cancer. In this study we evaluate seven TERT SNPs in 1555 incident colon cancer cases and 1956 matched controls and in 754 incident rectal cancer cases and 959 matched controls. We observed that two TERT SNPs were associated with colon cancer. TERT rs2736118 was associated with increased risk of colon cancer (OR = 1.31, 95% CI 1.02, 1.69) and TERT-CLPTM1L rs2853668 was inversely associated with colon cancer (OR = 0.71, 95% CI 0.55, 0.92). TERT-CLPTM1L rs2853668 also was inversely associated with rectal cancer (OR 0.62, 95% CI 0.43, 0.90). BMI interacted significantly with three TERT SNPs to alter risk of colon cancer. Those with the variant allele and who were obese had the greatest risk of colon cancer. TERT-CLPTM1L rs2853668 interacted significantly with aspirin/NSAID use, where those with the AA genotype had a much lower risk of colon cancer when using aspirin/NSAIDs than those with the other genotypes. Several TERT SNPs were uniquely associated with CIMP+ and MSI tumors. These data confirm earlier reports of the association between TERT-CLPTM1L and colon and rectal cancer. Our detection of a significant interaction with BMI for multiple TERT SNPs and unique associations with CIMP+ tumors enhance our understanding of TERT's role in colon carcinogenesis. 22351525 0 4 TERT Gene 7015 22351525 15 40 colorectal carcinogenesis Disease 1 22351525 0 32 Telomerase reverse transcriptase Gene 7015 22351525 34 38 TERT Gene 7015 22351525 178 182 TERT Gene 7015 22351525 219 236 colorectal cancer Disease D015179 22351525 270 274 TERT Gene 7015 22351525 297 309 colon cancer Disease D003110 22351525 369 375 cancer Disease D009369 22351525 429 433 TERT Gene 7015 22351525 460 472 colon cancer Disease D003110 22351525 474 478 TERT Gene 7015 22351525 527 539 colon cancer Disease D003110 22351525 575 579 TERT Gene 7015 22351525 580 587 CLPTM1L Gene 81037 22351525 628 640 colon cancer Disease D003110 22351525 673 677 TERT Gene 7015 22351525 678 685 CLPTM1L Gene 81037 22351525 738 744 cancer Disease D009369 22351525 775 778 BMI Environment 7015-D003110 22351525 815 819 TERT Gene 7015 22351525 842 854 colon cancer Disease D003110 22351525 899 904 obese Disease D009765 22351525 899 904 obese Environment 81037-D003110 22351525 899 904 obese Environment 7015-D003110 22351525 930 942 colon cancer Disease D003110 22351525 944 948 TERT Gene 7015 22351525 949 956 CLPTM1L Gene 81037 22351525 997 1014 aspirin/NSAID use Environment 81037-D003110 22351525 997 1014 aspirin/NSAID use Environment 7015-D003110 22351525 1074 1086 colon cancer Disease D003110 22351525 1098 1112 aspirin/NSAIDs Environment 81037-D003110 22351525 1098 1112 aspirin/NSAIDs Environment 7015-D003110 22351525 1158 1162 TERT Gene 7015 22351525 1212 1218 tumors Disease D009369 22351525 1282 1286 TERT Gene 7015 22351525 1287 1294 CLPTM1L Gene 81037 22351525 1316 1322 cancer Disease D009369 22351525 1372 1375 BMI Environment 7015-D003110 22351525 1389 1393 TERT Gene 7015 22351525 1434 1440 tumors Disease D009369 22351525 1470 1474 TERT Gene 7015 22351525 1485 1505 colon carcinogenesis Disease D003110 18586686|t|Peroxisome proliferator-activated receptor-alpha (PPARA) genetic polymorphisms and breast cancer risk: a Long Island ancillary study. 18586686|t|Peroxisome proliferator-activated receptor-alpha (PPARA) has been shown to increase fatty acid oxidation and decrease cytokine levels and has been implicated in insulin production. Genetic variants of PPARA have been associated with cardiovascular disease, obesity and type II diabetes mellitus. Although no research to date has investigated the possible link between PPARA and breast cancer, the function of this gene suggests that it could play a role in breast cancer development. Six PPARA polymorphisms were evaluated in association with incident breast cancer in a population-based case-control study (n = 1073 cases and n = 1112 controls) using unconditional logistic and multilevel regression and haplotype-based analyses. The odds of breast cancer were doubled among women with PPARA polymorphism rs4253760 (odds ratio = 1.97 for rare versus common homozygote alleles; 95% confidence interval: 1.14, 3.43). This association remained constant with the inclusion of all interrogated polymorphisms studied in hierarchical models. No additive interactions with body mass index or weight gain were present, but there was some evidence of interaction between PPARA variants and aspirin use, defined as use at least once per week for 6 months or longer. Fourteen haplotypes were imputed with frequencies >1% among postmenopausal women, but no statistically significant differences in haplotype frequencies between cases and controls were evident. Our results are the first to evaluate the relationship between PPARA and breast cancer incidence and suggest that replication in an independent cohort is warranted. 18586686 0 48 Peroxisome proliferator-activated receptor-alpha Gene 5465 18586686 50 55 PPARA Gene 5465 18586686 83 96 breast cancer Disease D001943 18586686 0 48 Peroxisome proliferator-activated receptor-alpha Gene 5465 18586686 50 55 PPARA Gene 5465 18586686 201 206 PPARA Gene 5465 18586686 233 255 cardiovascular disease Disease D002318 18586686 257 264 obesity Disease D009765 18586686 269 294 type II diabetes mellitus Disease D003924 18586686 368 373 PPARA Gene 5465 18586686 378 391 breast cancer Disease D001943 18586686 457 470 breast cancer Disease D001943 18586686 488 493 PPARA Gene 5465 18586686 552 565 breast cancer Disease D001943 18586686 743 756 breast cancer Disease D001943 18586686 787 792 PPARA Gene 5465 18586686 1085 1096 weight gain Disease D015430 18586686 1162 1167 PPARA Gene 5465 18586686 1181 1192 aspirin use Environment 5465-D001943 18586686 1205 1254 use at least once per week for 6 months or longer Environment 5465-D001943 18586686 1512 1517 PPARA Gene 5465 18586686 1522 1535 breast cancer Disease D001943 14973091|t|MTHFR polymorphisms, dietary folate intake, and breast cancer risk: results from the Shanghai Breast Cancer Study. 14973091|t|Folate plays an important role in DNA methylation, synthesis, and repair; intake has been associated with breast cancer. The folate-metabolizing enzyme, methylenetetrahydrofolate reductase (MTHFR) is polymorphic at nucleotides 677 (C-->T) and 1298 (A-->C), resulting in allozymes with decreased activity. We evaluated these two common polymorphisms and their effects on the folate intake and breast cancer risk association in a population-based case-control study of 1144 breast cancer cases and 1236 controls using a PCR-RFLP-based assay. All subjects completed in-person interviews, which included a food frequency questionnaire. Unconditional logistic regression models were used to calculate odds ratios and their 95% confidence intervals, after adjusting for potential confounding factors. Cases and controls were similar in the distribution of MTHFR polymorphisms at codons 677 (41.4% cases and 41.8% controls carried the T allele) and 1298 (17.6% cases and 17.5% controls carried the C allele). An inverse association of breast cancer risk with folate intake was observed in all genotype groups, particularly among subjects with the 677TT genotype. Compared with those with the 677CC genotype and high folate, the adjusted odds ratios (95% confidence intervals) associated with low folate intake were 1.94 (1.15-3.26), 2.17 (1.34-3.51), and 2.51 (1.37-4.60) for subjects who had CC, CT, and TT genotypes (p for interaction, 0.05). No modifying effect of A1298C genotypes on the association of folate intake with breast cancer risk was observed. Results of this study suggest that the MTHFR C677T polymorphisms may modify the association between dietary folate intake and breast cancer risk. 14973091 0 5 MTHFR Gene 4524 14973091 48 61 breast cancer Disease D001943 14973091 106 119 breast cancer Disease D001943 14973091 153 188 methylenetetrahydrofolate reductase Gene 4524 14973091 190 195 MTHFR Gene 4524 14973091 392 405 breast cancer Disease D001943 14973091 472 485 breast cancer Disease D001943 14973091 850 855 MTHFR Gene 4524 14973091 1028 1041 breast cancer Disease D001943 14973091 1052 1065 folate intake Environment 4524-D001943 14973091 1285 1302 low folate intake Environment 4524-D001943 14973091 1519 1532 breast cancer Disease D001943 14973091 1591 1596 MTHFR Gene 4524 14973091 1652 1673 dietary folate intake Environment 4524-D001943 14973091 1678 1691 breast cancer Disease D001943 21082260|t|Genetic polymorphisms of glutathione S-transferase M1 and bladder cancer risk: a meta-analysis of 26 studies. 21082260|t|Studies investigating the association between glutathione S-transferase M1 (GSTM1) polymorphism and bladder cancer risk report conflicting results. The objective of this study was to quantitatively summarize the evidence for such a relationship. We performed a systematic search of the National Library of Medline and Embase databases. This meta-analysis included 26 case-control studies, which included 5029 bladder cancer cases and 6680 controls. The combined results based on all studies showed that the GSTM1 null genotype was associated with an increased risk of bladder cancer (OR=1.46, 95% confidence interval [CI]=1.35, 1.57). When stratifying for race, results were similar among Asians (OR=1.60, 95% CI=1.27, 2.01) and Caucasians (OR=1.44, 95% CI=1.33, 1.57) except Africans (OR=1.25, 95% CI=0.76, 2.06). When stratifying by the smoking, stage, grade, and histological type of bladder cancer, we found no statistical association. Our meta-analysis suggests that the GSTM1 null genotype is associated with a modest increase in the risk of bladder cancer. 21082260 25 53 glutathione S-transferase M1 Gene 2944 21082260 58 72 bladder cancer Disease D001749 21082260 46 74 glutathione S-transferase M1 Gene 2944 21082260 76 81 GSTM1 Gene 2944 21082260 100 114 bladder cancer Disease D001749 21082260 409 423 bladder cancer Disease D001749 21082260 507 512 GSTM1 Gene 2944 21082260 568 582 bladder cancer Disease D001749 21082260 689 695 Asians Environment 2944-D001749 21082260 729 739 Caucasians Environment 2944-D001749 21082260 887 901 bladder cancer Disease D001749 21082260 976 981 GSTM1 Gene 2944 21082260 1048 1062 bladder cancer Disease D001749 23404351|t|Genetic variation in the lipoxygenase pathway and risk of colorectal neoplasia. 23404351|t|Arachidonate lipoxygenase (ALOX) enzymes metabolize arachidonic acid to generate potent inflammatory mediators and play an important role in inflammation-associated diseases. We investigated associations between colorectal cancer risk and polymorphisms in ALOX5, FLAP, ALOX12, and ALOX15, and their interactions with nonsteroidal anti-inflammatory drug (NSAID) use. We genotyped fifty tagSNPs, one candidate SNP, and two functional promoter variable nucleotide tandem repeat (VNTR) polymorphisms in three US population-based case-control studies of colon cancer (1,424 cases/1,780 controls), rectal cancer (583 cases/775 controls), and colorectal adenomas (485 cases/578 controls). Individuals with variant genotypes of the ALOX5 VNTR had a decreased risk of rectal cancer, with the strongest association seen for individuals with one or more alleles of >5 repeats (wild type = 5, OR>5/>/=5 = 0.42, 95% CI 0.20-0.92; P = 0.01). Four SNPs in FLAP (rs17239025), ALOX12 (rs2073438), and ALOX15 (rs4796535 and rs2619112) were associated with rectal cancer risk at P A polymorphism associated with gastric cancer among Asians but not Europeans. 21214416|t|UNLABELLED: E-cadherin (CDH1) is a tumor suppressor gene involved in epithelial cell-cell interactions and plays important roles in the etiology of gastric cancer. Studies reporting conflicting results on the role of -160C>A polymorphism in the CDH1 promoter region on gastric cancer risk led us to perform a meta-analysis to investigate this relationship. Thirteen published case-control studies including 2509 gastric cancer cases and 3687 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. Overall, individuals with the variant genotypes were not associated with a significant gastric cancer risk (AA vs. CC: OR = 1.04, 95% CI: 0.74-1.48; CA vs. CC: 1.02, 0.85-1.21; AA/CA vs. CC: 1.03, 0.86-1.22; AA vs. CA/CC: 1.03, 0.74-1.43). However, in the stratified analysis by ethnicity, significantly decreased gastric cancer risk was found among Asians in dominant model (AA/CA vs. CC: 0.84, 0.72-0.99). Further, when stratified by clinicopathologic characteristics of gastric cancer, no statistically significant result was observed for any analysis. The results suggested that the CDH1 -160C>A polymorphism may contribute to susceptibility to gastric cancer among Asians. Additional well-designed large studies will be required to validate this association in different populations. 21214416 4 14 E-cadherin Gene 999 21214416 16 20 CDH1 Gene 999 21214416 59 73 gastric cancer Disease D013274 21214416 80 86 Asians Environment 999-D013274 21214416 12 22 E-cadherin Gene 999 21214416 24 28 CDH1 Gene 999 21214416 35 40 tumor Disease D009369 21214416 148 162 gastric cancer Disease D013274 21214416 245 249 CDH1 Gene 999 21214416 269 283 gastric cancer Disease D013274 21214416 412 426 gastric cancer Disease D013274 21214416 661 675 gastric cancer Disease D013274 21214416 888 902 gastric cancer Disease D013274 21214416 924 930 Asians Environment 999-D013274 21214416 1047 1061 gastric cancer Disease D013274 21214416 1161 1165 CDH1 Gene 999 21214416 1223 1237 gastric cancer Disease D013274 21214416 1244 1250 Asians Environment 999-D013274 16014702|t|MGMT genotype modulates the associations between cigarette smoking, dietary antioxidants and breast cancer risk. 16014702|t|O(6)-methylguanine DNA methyl-transferase (MGMT) is the only known critical gene involved in cellular defense against alkylating agents in the DNA direct reversal repair (DRR) pathway. Three single nucleotide polymorphism (SNP) coding for non-conservative amino acid substitutions have been identified [C250T (Leu84Phe), A427G (Ile143Val) and A533G (Lys178Arg)]. To examine the importance of the DRR pathway in risk for breast cancer and the potential interaction with cigarette smoking and dietary antioxidants, we genotyped for these variants using biospecimens from the Long Island Breast Cancer Study Project. Genotyping was performed by a high throughput assay with fluorescence polarization and included 1067 cases and 1110 controls. Overall, there was no main effect between any variant genotype, haplotype or diplotype and breast cancer risk. Heavy smoking (>31 pack-year) significantly increased breast cancer risk for women with the codon 84 variant T-allele [odds ratio, OR = 3.0, 95% confidence interval (95% CI) = 1.4-6.2]. An inverse association between fruits and vegetables consumption and breast cancer risk was observed among women with the wild-type genotype for codon 84 (OR = 0.8, 95% CI = 0.6-0.9 for > or =35 servings of fruits and vegetables per week and CC genotype versus those with <35 servings per week and CC genotype). The association between fruits and vegetables consumption and reduced breast cancer risk was apparent among women with at least one variant allele for codon 143 (OR = 0.6, 95% CI = 0.5-0.9 for > or =35 servings of fruits and vegetables per week and AG or GG genotype versus those with <35 servings per week and AA genotype). Similar patterns were observed for dietary alpha-carotene and supplemental beta-carotene, but not for supplemental vitamins C and E. These data suggest that polymorphisms in MGMT may modulate the inverse association previously observed between fruits and vegetables consumption, dietary antioxidants and breast cancer risk, and support the importance of fruits and vegetables on breast cancer risk reduction. 16014702 0 4 MGMT Gene 4255 16014702 49 66 cigarette smoking Environment 4255-D001943 16014702 68 88 dietary antioxidants Environment 4255-D001943 16014702 93 106 breast cancer Disease D001943 16014702 0 41 O(6)-methylguanine DNA methyl-transferase Gene 4255 16014702 43 47 MGMT Gene 4255 16014702 420 433 breast cancer Disease D001943 16014702 831 844 breast cancer Disease D001943 16014702 851 880 Heavy smoking (>31 pack-year) Environment 4255-D001943 16014702 905 918 breast cancer Disease D001943 16014702 1068 1101 fruits and vegetables consumption Environment 4255-D001943 16014702 1106 1119 breast cancer Disease D001943 16014702 1223 1274 > or =35 servings of fruits and vegetables per week Environment 4255-D001943 16014702 1373 1406 fruits and vegetables consumption Environment 4255-D001943 16014702 1419 1432 breast cancer Disease D001943 16014702 1542 1593 > or =35 servings of fruits and vegetables per week Environment 4255-D001943 16014702 1709 1731 dietary alpha-carotene Environment 4255-D001943 16014702 1736 1762 supplemental beta-carotene Environment 4255-D001943 16014702 1848 1852 MGMT Gene 4255 16014702 1918 1951 fruits and vegetables consumption Environment 4255-D001943 16014702 1953 1973 dietary antioxidants Environment 4255-D001943 16014702 1978 1991 breast cancer Disease D001943 16014702 2028 2034 fruits Environment 4255-D001943 16014702 2039 2049 vegetables Environment 4255-D001943 16014702 2053 2066 breast cancer Disease D001943 26976855|t|Assessment of Multifactor Gene-Environment Interactions and Ovarian Cancer Risk: Candidate Genes, Obesity, and Hormone-Related Risk Factors. 26976855|t|BACKGROUND: Many epithelial ovarian cancer (EOC) risk factors relate to hormone exposure and elevated estrogen levels are associated with obesity in postmenopausal women. Therefore, we hypothesized that gene-environment interactions related to hormone-related risk factors could differ between obese and non-obese women. METHODS: We considered interactions between 11,441 SNPs within 80 candidate genes related to hormone biosynthesis and metabolism and insulin-like growth factors with six hormone-related factors (oral contraceptive use, parity, endometriosis, tubal ligation, hormone replacement therapy, and estrogen use) and assessed whether these interactions differed between obese and non-obese women. Interactions were assessed using logistic regression models and data from 14 case-control studies (6,247 cases; 10,379 controls). Histotype-specific analyses were also completed. RESULTS: SNPs in the following candidate genes showed notable interaction: IGF1R (rs41497346, estrogen plus progesterone hormone therapy, histology = all, P = 4.9 x 10(-6)) and ESR1 (rs12661437, endometriosis, histology = all, P = 1.5 x 10(-5)). The most notable obesity-gene-hormone risk factor interaction was within INSR (rs113759408, parity, histology = endometrioid, P = 8.8 x 10(-6)). CONCLUSIONS: We have demonstrated the feasibility of assessing multifactor interactions in large genetic epidemiology studies. Follow-up studies are necessary to assess the robustness of our findings for ESR1, CYP11A1, IGF1R, CYP11B1, INSR, and IGFBP2 Future work is needed to develop powerful statistical methods able to detect these complex interactions. IMPACT: Assessment of multifactor interaction is feasible, and, here, suggests that the relationship between genetic variants within candidate genes and hormone-related risk factors may vary EOC susceptibility. Cancer Epidemiol Biomarkers Prev; 25(5); 780-90. (c)2016 AACR. 26976855 60 74 Ovarian Cancer Disease D010051 26976855 98 105 Obesity Disease D009765 26976855 17 42 epithelial ovarian cancer Disease C538090 26976855 44 47 EOC Disease C538090 26976855 138 145 obesity Disease D009765 26976855 294 299 obese Disease D009765 26976855 308 313 obese Disease D009765 26976855 548 561 endometriosis Disease D004715 26976855 683 688 obese Disease D009765 26976855 697 702 obese Disease D009765 26976855 964 969 IGF1R Gene 3480 26976855 1066 1070 ESR1 Gene 2099 26976855 1084 1097 endometriosis Disease D004715 26976855 1152 1159 obesity Disease D009765 26976855 1152 1159 obesity Environment 3643-C538090 26976855 1152 1159 obesity Environment 2099-C538090 26976855 1152 1159 obesity Environment 3480-C538090 26976855 1208 1212 INSR Gene 3643 26976855 1484 1488 ESR1 Gene 2099 26976855 1490 1497 CYP11A1 Gene 1583 26976855 1499 1504 IGF1R Gene 3480 26976855 1506 1513 CYP11B1 Gene 1584 26976855 1515 1519 INSR Gene 3643 26976855 1525 1531 IGFBP2 Gene 3485 26976855 1828 1831 EOC Disease C538090 26976855 1848 1854 Cancer Disease D009369 26976855 1898 1904 c)2016 Gene 1036088 20564069|t|Mediating effects of smoking and chronic obstructive pulmonary disease on the relation between the CHRNA5-A3 genetic locus and lung cancer risk. 20564069|t|BACKGROUND: Recent genome-wide association studies of lung cancer have shown that the CHRNA5-A3 region on chromosome 15q24-25.1 is strongly associated with an increased risk of lung cancer and nicotine dependence, and is thought to be associated with chronic obstructive pulmonary disease as well. However, it has not been established whether the association between genetic variants and lung cancer risk is a direct one or one mediated by nicotine dependence. METHODS: The authors applied a rigorous statistical approach, mediation analysis, to examine the mediating effect of smoking behavior and self-reported, physician-diagnosed emphysema (chronic obstructive pulmonary disease [COPD]) on the relation between the CHRNA5-A3 region genetic variant rs1051730 and the risk of lung cancer. RESULTS: Our results showed that rs1051730 is directly associated with lung cancer risk, but it is also associated with lung cancer risk through its effect on both smoking behavior and COPD. Furthermore, we showed that COPD is a mediating phenotype that explains part of the effect of smoking behavior on lung cancer. Our results also suggested that smoking behavior is a mediator of the relation between rs1051730 and COPD risk. CONCLUSIONS: Smoking behavior and COPD are mediators of the association between the single nucleotide polymorphism (SNP) rs1051730 and the risk of lung cancer. Also, COPD is a mediator of the association between smoking behavior and lung cancer. Finally, smoking behavior also has mediating effects on the association between the SNP and COPD. 20564069 21 28 smoking Environment 1138-D008175 20564069 33 70 chronic obstructive pulmonary disease Disease D029424 20564069 33 70 chronic obstructive pulmonary disease Environment 1138-D008175 20564069 99 105 CHRNA5 Gene 1138 20564069 127 138 lung cancer Disease D008175 20564069 54 65 lung cancer Disease D008175 20564069 86 92 CHRNA5 Gene 1138 20564069 177 188 lung cancer Disease D008175 20564069 193 212 nicotine dependence Disease D014029 20564069 251 288 chronic obstructive pulmonary disease Disease D029424 20564069 388 399 lung cancer Disease D008175 20564069 440 459 nicotine dependence Disease D014029 20564069 634 643 emphysema Disease D004646 20564069 645 682 chronic obstructive pulmonary disease Disease D029424 20564069 684 688 COPD Gene 260431 20564069 684 688 COPD Disease D029424 20564069 719 725 CHRNA5 Gene 1138 20564069 778 789 lung cancer Disease D008175 20564069 862 873 lung cancer Disease D008175 20564069 911 922 lung cancer Disease D008175 20564069 950 980 both smoking behavior and COPD Environment 1138-D008175 20564069 976 980 COPD Gene 260431 20564069 976 980 COPD Disease D029424 20564069 1010 1014 COPD Gene 260431 20564069 1010 1014 COPD Disease D029424 20564069 1096 1107 lung cancer Disease D008175 20564069 1210 1214 COPD Gene 260431 20564069 1210 1214 COPD Disease D029424 20564069 1234 1250 Smoking behavior Environment 1138-D008175 20564069 1255 1259 COPD Gene 260431 20564069 1255 1259 COPD Disease D029424 20564069 1255 1259 COPD Environment 1138-D008175 20564069 1368 1379 lung cancer Disease D008175 20564069 1387 1391 COPD Gene 260431 20564069 1387 1391 COPD Disease D029424 20564069 1454 1465 lung cancer Disease D008175 20564069 1559 1563 COPD Gene 260431 20564069 1559 1563 COPD Disease D029424 18922928|t|A SNP in a let-7 microRNA complementary site in the KRAS 3' untranslated region increases non-small cell lung cancer risk. 18922928|t|Lung cancer is the leading cause of cancer deaths worldwide, yet few genetic markers of lung cancer risk useful for screening exist. The let-7 family-of-microRNAs (miRNA) are global genetic regulators important in controlling lung cancer oncogene expression by binding to the 3' untranslated regions of their target mRNAs. The purpose of this study was to identify single nucleotide polymorphisms (SNP) that could modify let-7 binding and to assess the effect of such SNPs on target gene regulation and risk for non-small cell lung cancer (NSCLC). let-7 complementary sites (LCS) were sequenced in the KRAS 3' untranslated region from 74 NSCLC cases to identify mutations and SNPs that correlated with NSCLC. The allele frequency of a previously unidentified SNP at LCS6 was characterized in 2,433 people (representing 46 human populations). The frequency of the variant allele is 18.1% to 20.3% in NSCLC patients and 5.8% in world populations. The association between the SNP and the risk for NSCLC was defined in two independent case-control studies. A case-control study of lung cancer from New Mexico showed a 2.3-fold increased risk (confidence interval, 1.1-4.6; P = 0.02) for NSCLC cancer in patients who smoked <40 pack-years. This association was validated in a second independent case-control study. Functionally, the variant allele results in KRAS overexpression in vitro. The LCS6 variant allele in a KRAS miRANA complementary site is significantly associated with increased risk for NSCLC among moderate smokers and represents a new paradigm for let-7 miRNAs in lung cancer susceptibility. 18922928 52 56 KRAS Gene 3845 18922928 90 116 non-small cell lung cancer Disease D002289 18922928 0 11 Lung cancer Disease D008175 18922928 88 99 lung cancer Disease D008175 18922928 226 237 lung cancer Disease D008175 18922928 512 538 non-small cell lung cancer Disease D002289 18922928 540 545 NSCLC Disease D002289 18922928 602 606 KRAS Gene 3845 18922928 638 643 NSCLC Disease D002289 18922928 702 707 NSCLC Disease D002289 18922928 899 904 NSCLC Disease D002289 18922928 994 999 NSCLC Disease D002289 18922928 1077 1088 lung cancer Disease D008175 18922928 1183 1195 NSCLC cancer Disease 1 18922928 1199 1233 patients who smoked <40 pack-years Environment 3845-D002289 18922928 1354 1358 KRAS Gene 3845 18922928 1413 1417 KRAS Gene 3845 18922928 1496 1501 NSCLC Disease D002289 18922928 1508 1524 moderate smokers Environment 3845-D002289 18922928 1575 1586 lung cancer Disease D008175 16614098|t|Is the association between cigarette smoking and breast cancer modified by genotype? A review of epidemiologic studies and meta-analysis. 16614098|t|Epidemiologic studies have examined the association between cigarette smoking and breast cancer risk according to genotype with increasing frequency, commensurate with the growing awareness of the roles genes play in detoxifying or activating chemicals found in cigarette smoke and in preventing or repairing the damage caused by those compounds. To date, approximately 50 epidemiologic studies have examined the association between smoking and breast cancer risk according to variation in genes related to carcinogen metabolism, modulation of oxidative damage, and DNA repair. Some of the findings presented here suggest possible effect modification by genotype. In particular, 14 epidemiologic studies have tended to show positive associations with long-term smoking among NAT2 slow acetylators, especially among postmenopausal women. Summary analyses produced overall meta-relative risk (RR) estimates for smoking of 1.2 [95% confidence interval (95% CI), 1.0-1.5] for rapid acetylators and 1.5 (95% CI, 1.2-1.8) for slow acetylators. After stratification by menopausal status, the meta-RR for postmenopausal slow acetylators was 2.4 (95% CI, 1.7-3.3), whereas similar analyses for the other categories showed no association. In addition, summary analyses produced meta-RRs for smoking of 1.1 (95% CI, 0.8-1.4) when GSTM1 was present and 1.5 (95% CI, 1.1-2.1) when the gene was deleted. Overall, however, interpretation of the available literature is complicated by methodologic limitations, including small sample sizes, varying definitions of smoking, and difficulties involving single nucleotide polymorphism selection, which likely have contributed to the inconsistent findings. These methodologic issues should be addressed in future studies to help clarify the association between smoking and breast cancer. 16614098 49 62 breast cancer Disease D001943 16614098 82 95 breast cancer Disease D001943 16614098 445 458 breast cancer Disease D001943 16614098 751 768 long-term smoking Environment 10-D001943 16614098 775 779 NAT2 Gene 10 16614098 909 916 smoking Environment 10-D001943 16614098 1097 1128 postmenopausal slow acetylators Environment 10-D001943 16614098 1281 1288 smoking Environment 10-D001943 16614098 1319 1324 GSTM1 Gene 2944 16614098 1802 1815 breast cancer Disease D001943