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Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia.

ABSTRACT: Genome-wide association studies (GWAS) have identified a large number of cancer-associated single nucleotide polymorphisms (SNPs), several of which have been associated with multiple cancer sites suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesized that SNPs associated with other cancers may be additionally associated with endometrial cancer. We examined 213 SNPs previously associated with 14 other cancers for their associations with endometrial cancer in 3758 endometrial cancer cases and 5966 controls of European ancestry from two consortia: Population Architecture Using Genomics and Epidemiology and the Epidemiology of Endometrial Cancer Consortium. Study-specific logistic regression estimates adjusted for age, body mass index and the most significant principal components of genetic ancestry were combined using fixed-effect meta-analysis to evaluate the association between each SNP and endometrial cancer risk. A Bonferroni-corrected P value of 2.35×10(-4) was used to determine statistical significance of the associations. SNP rs7679673, ~6.3kb upstream of TET2 and previously reported to be associated with prostate cancer risk, was associated with endometrial cancer risk in the direction opposite to that for prostate cancer [meta-analysis odds ratio = 0.87 (per copy of the C allele), 95% confidence interval = 0.81, 0.93; P = 7.37×10(-5)] with no evidence of heterogeneity across studies (P heterogeneity = 0.66). This pleiotropic analysis is the first to suggest TET2 as a susceptibility locus for endometrial cancer.

SUBMITTER: Setiawan VW

PROVIDER: S-EPMC4146418 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia.

Setiawan Veronica Wendy VW Schumacher Fredrick F Prescott Jennifer J Haessler Jeffrey J Malinowski Jennifer J Wentzensen Nicolas N Yang Hannah H Chanock Stephen S Brinton Louise L Hartge Patricia P Lissowska Jolanta J Park S Lani SL Cheng Iona I Bush William S WS Crawford Dana C DC Ursin Giske G Horn-Ross Pamela P Bernstein Leslie L Lu Lingeng L Risch Harvey H Yu Herbert H Sakoda Lori C LC Doherty Jennifer J Chen Chu C Jackson Rebecca R Yasmeen Shagufta S Cote Michele M Kocarnik Jonathan M JM Peters Ulrike U Kraft Peter P De Vivo Immaculata I Haiman Christopher A CA Kooperberg Charles C Le Marchand Loic L

Carcinogenesis 20140515 9

Genome-wide association studies (GWAS) have identified a large number of cancer-associated single nucleotide polymorphisms (SNPs), several of which have been associated with multiple cancer sites suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesized that SNPs associated with other cancers may be additionally associated with endometrial cancer. We examined 213 SNPs previously associated with 14 other cancers for their associations with endometrial ca ...[more]

PMID: 24832084

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Project description:BackgroundEpidemiologic studies suggest that coffee consumption may be inversely associated with risk of endometrial cancer (EC), the most common gynecological malignancy in developed countries. Furthermore, coffee consumption may lower circulating concentrations of estrogen and insulin, hormones implicated in endometrial carcinogenesis. Antioxidants and other chemopreventive compounds in coffee may have anticarcinogenic effects. Based on available meta-analyses, the World Cancer Research Fund (WCRF) concluded that consumption of coffee probably protects against EC.ObjectivesOur main aim was to examine the association between coffee consumption and EC risk by combining individual-level data in a pooled analysis. We also sought to evaluate potential effect modification by other risk factors for EC.MethodsWe combined individual-level data from 19 epidemiologic studies (6 cohort, 13 case-control) of 12,159 EC cases and 27,479 controls from the Epidemiology of Endometrial Cancer Consortium (E2C2). Logistic regression was used to calculate ORs and their corresponding 95% CIs. All models were adjusted for potential confounders including age, race, BMI, smoking status, diabetes status, study design, and study site.ResultsCoffee drinkers had a lower risk of EC than non-coffee drinkers (multiadjusted OR: 0.87; 95% CI: 0.79, 0.95). There was a dose-response relation between higher coffee consumption and lower risk of EC: compared with non-coffee drinkers, the adjusted pooled ORs for those who drank 1, 2-3, and >4 cups/d were 0.90 (95% CI: 0.82, 1.00), 0.86 (95% CI: 0.78, 0.95), and 0.76 (95% CI: 0.66, 0.87), respectively (P-trend < 0.001). The inverse association between coffee consumption and EC risk was stronger in participants with BMI > 25 kg/m2.ConclusionsThe results of the largest analysis to date pooling individual-level data further support the potentially beneficial health effects of coffee consumption in relation to EC, especially among females with higher BMI.

Dataset Information

Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia.

Publications

Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia.

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