HNF1B and Endometrial Cancer Risk: Results from the PAGE studyReport as inadecuate

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We examined the association between HNF1B variants identified in a recent genome-wide association study and endometrial cancer in two large case-control studies nested in prospective cohorts: the Multiethnic Cohort Study MEC and the Women-s Health Initiative WHI as part of the Population Architecture using Genomics and Epidemiology PAGE study. A total of 1,357 incident cases of invasive endometrial cancer and 7,609 controls were included in the analysis MEC: 426 cases-3,854 controls; WHI: 931cases-3,755 controls. The majority of women in the WHI were European American, while the MEC included sizable numbers of African Americans, Japanese and Latinos. We estimated the odds ratios ORs per allele and 95% confidence intervals CIs of each SNP using unconditional logistic regression adjusting for age, body mass index, and four principal components of ancestry informative markers. The combined ORs were estimated using fixed effect models. Rs4430796 and rs7501939 were associated with endometrial cancer risk in MEC and WHI with no heterogeneity observed across racial-ethnic groups P≥0.21 or between studies P≥0.70. The ORper allele was 0.82 95% CI: 0.75, 0.89; P = 5.63×10−6 for rs4430796 G allele and 0.79 95% CI: 0.73, 0.87; P = 3.77×10−7 for rs7501939 A allele. The associations with the risk of Type I and Type II tumors were similar P≥0.19. Adjustment for additional endometrial cancer risk factors such as parity, oral contraceptive use, menopausal hormone use, and smoking status had little effect on the results. In conclusion, HNF1B SNPs are associated with risk of endometrial cancer and that the associated relative risks are similar for Type I and Type II tumors.

Author: Veronica Wendy Setiawan, Jeffrey Haessler, Fredrick Schumacher, Michele L. Cote, Ewa Deelman, Megan D. Fesinmeyer, Brian E. Hende



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