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

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

doi:10.1093/carcin/bgu107

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

Carcinogenesis. 2014 Sep;35(9):2068-73. doi: 10.1093/carcin/bgu107. Epub 2014 May 15.

Authors

Veronica Wendy Setiawan¹, Fredrick Schumacher², Jennifer Prescott³, Jeffrey Haessler⁴, Jennifer Malinowski⁵, Nicolas Wentzensen⁶, Hannah Yang⁶, Stephen Chanock⁶, Louise Brinton⁶, Patricia Hartge⁶, Jolanta Lissowska⁷, S Lani Park², Iona Cheng⁸, William S Bush⁵, Dana C Crawford⁵, Giske Ursin⁹, Pamela Horn-Ross⁸, Leslie Bernstein¹⁰, Lingeng Lu¹¹, Harvey Risch¹¹, Herbert Yu¹², Lori C Sakoda¹³, Jennifer Doherty¹⁴, Chu Chen⁴, Rebecca Jackson¹⁵, Shagufta Yasmeen¹⁶, Michele Cote¹⁷, Jonathan M Kocarnik⁴, Ulrike Peters⁴, Peter Kraft¹⁸, Immaculata De Vivo¹⁸, Christopher A Haiman², Charles Kooperberg⁴, Loic Le Marchand¹²

Affiliations

¹ Department 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.
² Department 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.
³ Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
⁴ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
⁵ Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37235, USA.
⁶ National Cancer Institute, Bethesda, MD 20892, USA.
⁷ M.Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 Warsaw, Poland.
⁸ Cancer Prevention Institute of California, Fremont, CA 94538, USA.
⁹ Institute of Population Based Cancer Research, Cancer Registry of Norway, N-0304 Oslo, Norway.
¹⁰ Division of Cancer Etiology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
¹¹ Department of Epidemiology, Yale School of Public Health, New Haven CT 06520, USA.
¹² Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
¹³ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA, Division of Research, Kaiser Permanente Northern California, Oakland, CA 94611, USA.
¹⁴ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA, Section of Biostatistics and Epidemiology, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, NH 03756, USA.
¹⁵ Division of Endocrinology, Diabetes and Metabolism, Ohio State University, Columbus, OH 43210, USA.
¹⁶ Department of Obstetrics and Gynecology, University of California, Davis, CA 95616, USA.
¹⁷ Department of Oncology, Wayne State University School of Medicine and Population Studies and Disparities Research, Karmanos Cancer Institute, Detroit, MI 48202, USA and.
¹⁸ Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA, Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.

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.

Publication types

Comparative Study
Meta-Analysis
Research Support, American Recovery and Reinvestment Act
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Case-Control Studies
DNA-Binding Proteins / genetics*
Dioxygenases
Endometrial Neoplasms / genetics*
Female
Genetic Pleiotropy
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Polymorphism, Single Nucleotide*
Proto-Oncogene Proteins / genetics*
Risk Factors

Substances

DNA-Binding Proteins
Proto-Oncogene Proteins
Dioxygenases
TET2 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding