title: Exome-wide association study of endometrial cancer in a multiethnic population.
abstract: Endometrial cancer (EC) contributes substantially to total burden of cancer morbidity and mortality in the United States. Family history is a known risk factor for EC, thus genetic factors may play a role in EC pathogenesis. Three previous genome-wide association studies (GWAS) have found only one locus associated with EC, suggesting that common variants with large effects may not contribute greatly to EC risk. Alternatively, we hypothesize that rare variants may contribute to EC risk. We conducted an exome-wide association study (EXWAS) of EC using the Infinium HumanExome BeadChip in order to identify rare variants associated with EC risk. We successfully genotyped 177,139 variants in a multiethnic population of 1,055 cases and 1,778 controls from four studies that were part of the Epidemiology of Endometrial Cancer Consortium (E2C2). No variants reached global significance in the study, suggesting that more power is needed to detect modest associations between rare genetic variants and risk of EC.
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Maxine M
authors.initials: MM
authors.lastname: Chen
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts, United States of America; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Marta
authors.initials: M
authors.lastname: Crous-Bou
authors.affiliation: University of Southern California, Los Angeles, California, United States of America.
authors.forename: Veronica W
authors.initials: VW
authors.lastname: Setiawan
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Prescott
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Sara H
authors.initials: SH
authors.lastname: Olson
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Amanda
authors.initials: A
authors.lastname: Black
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Louise
authors.initials: L
authors.lastname: Brinton
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Constance
authors.initials: C
authors.lastname: Chen
authors.affiliation: University of New Mexico, Albuquerque, New Mexico, United States of America; Alberta Health Services - CancerControl Alberta, Calgary, Alberta, Canada.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Cook
authors.affiliation: Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Doherty
authors.affiliation: Alberta Health Services - CancerControl Alberta, Calgary, Alberta, Canada.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Friedenreich
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; Department of Biostatistics and Epidemiology, University of Massachusetts, Amherst, Massachusetts, United States of America.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Patricia
authors.initials: P
authors.lastname: Hartge
authors.affiliation: University of Southern California, Los Angeles, California, United States of America.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.affiliation: University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America.
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Cancer Epidemiology and Prevention, M Sklodowska-Curie Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.affiliation: Yale University School of Public Health, New Haven, Connecticut, United States of America.
authors.forename: Lingeng
authors.initials: L
authors.lastname: Lu
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Irene
authors.initials: I
authors.lastname: Orlow
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Stacey
authors.initials: S
authors.lastname: Petruzella
authors.affiliation: Center for Cancer Prevention (CPO-Piemonte), Turin, Italy; Human Genetic Foundation (HuGeF), Turin, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Polidoro
authors.affiliation: University of Southern California, Los Angeles, California, United States of America.
authors.forename: Loreall
authors.initials: L
authors.lastname: Pooler
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
authors.affiliation: Yale University School of Public Health, New Haven, Connecticut, United States of America.
authors.forename: Harvey
authors.initials: H
authors.lastname: Risch
authors.affiliation: Center for Cancer Prevention (CPO-Piemonte), Turin, Italy; Human Genetic Foundation (HuGeF), Turin, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.affiliation: Cancer Prevention Institute of California, Fremont, California, United States of America.
authors.forename: Frederick
authors.initials: F
authors.lastname: Schumacher
authors.affiliation: University of Southern California, Los Angeles, California, United States of America.
authors.forename: Xin
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
authors.affiliation: University of Washington, Seattle, Seattle, Washington, United States of America.
authors.forename: Noel S
authors.initials: NS
authors.lastname: Weiss
authors.affiliation: University of Southern California, Los Angeles, California, United States of America.
authors.forename: Lucy
authors.initials: L
authors.lastname: Xia
authors.affiliation: University of Southern California, Los Angeles, California, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Van Den Berg
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Hannah P
authors.initials: HP
authors.lastname: Yang
authors.affiliation: University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America.
authors.forename: Herbert
authors.initials: H
authors.lastname: Yu
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.affiliation: University of Southern California, Los Angeles, California, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Haiman
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts, United States of America; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Immaculata
authors.initials: I
authors.lastname: De Vivo
mesh_terms: D000368:Aged; D016889:Endometrial Neoplasms / Q000208:ethnology* / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged