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Published on: September 12, 2019
Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia
Veronica Wendy Setiawan1, Fredrick Schumacher2, Jennifer Prescott3
1Department of Preventive Medicine, Keck School of Medicine, and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA, Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37235, USA, National Cancer Institute, Bethesda, MD 20892, USA, M.Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 Warsaw, Poland, Cancer Prevention Institute of California, Fremont, CA 94538, USA, Institute of Population Based Cancer Research, Cancer Registry of Norway, N-0304 Oslo, Norway, Division of Cancer Etiology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA, Department of Epidemiology, Yale School of Public Health, New Haven CT 06520, USA, Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA, Division of Research, Kaiser Permanente Northern California, Oakland, CA 94611, USA, Section of Biostatistics and Epidemiology, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, NH 03756, USA, Division of Endocrinology, Diabetes and Metabolism, Ohio State University, Columbus, OH 43210, USA, Department of Obstetrics and Gynecology, University of California, Davis, CA 95616, USA, Department of Oncology, Wayne State University School of Medicine and Population Studies and Disparities Research, Karmanos Cancer Institute, Detroit, MI 48202, USA and Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA vsetiawa@usc.edu.
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.
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