title: Body Mass Index Genetic Risk Score and Endometrial Cancer Risk.
abstract: Genome-wide association studies (GWAS) have identified common variants that predispose individuals to a higher body mass index (BMI), an independent risk factor for endometrial cancer. Composite genotype risk scores (GRS) based on the joint effect of published BMI risk loci were used to explore whether endometrial cancer shares a genetic background with obesity. Genotype and risk factor data were available on 3,376 endometrial cancer case and 3,867 control participants of European ancestry from the Epidemiology of Endometrial Cancer Consortium GWAS. A BMI GRS was calculated by summing the number of BMI risk alleles at 97 independent loci. For exploratory analyses, additional GRSs were based on subsets of risk loci within putative etiologic BMI pathways. The BMI GRS was statistically significantly associated with endometrial cancer risk (P = 0.002). For every 10 BMI risk alleles a woman had a 13% increased endometrial cancer risk (95% CI: 4%, 22%). However, after adjusting for BMI, the BMI GRS was no longer associated with risk (per 10 BMI risk alleles OR = 0.99, 95% CI: 0.91, 1.07; P = 0.78). Heterogeneity by BMI did not reach statistical significance (P = 0.06), and no effect modification was noted by age, GWAS Stage, study design or between studies (P≥0.58). In exploratory analyses, the GRS defined by variants at loci containing monogenic obesity syndrome genes was associated with reduced endometrial cancer risk independent of BMI (per BMI risk allele OR = 0.92, 95% CI: 0.88, 0.96; P = 2.1 x 10-5). Possessing a large number of BMI risk alleles does not increase endometrial cancer risk above that conferred by excess body weight among women of European descent. Thus, the GRS based on all current established BMI loci does not provide added value independent of BMI. Future studies are required to validate the unexpected observed relation between monogenic obesity syndrome genetic variants and endometrial cancer risk.
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.|Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Prescott
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Veronica W
authors.initials: VW
authors.lastname: Setiawan
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, United States of America.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Fredrick
authors.initials: F
authors.lastname: Schumacher
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America.|Department of Epidemiology and Public Health, Yale Cancer Center, Yale School of Public Health, New Haven, Connecticut, United States of America.
authors.forename: Herbert
authors.initials: H
authors.lastname: Yu
authors.affiliation: Division of Epidemiology, Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Ryan
authors.initials: R
authors.lastname: Delahanty
authors.affiliation: Beckman Research Institute, City of Hope, Duarte, California, United States of America.
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, United States of America.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center and Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, United States of America.
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.affiliation: University of New Mexico, Albuquerque, New Mexico, United States of America.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Cook
authors.affiliation: Division of Cancer Care, Department of Population Health Research, Alberta Health Services-Cancer Control Alberta, Calgary, Alberta, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Friedenreich
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, United Kingdom.
authors.forename: Monserrat
authors.initials: M
authors.lastname: Garcia-Closas
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.affiliation: Epidemiology Program, 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 Epidemiology and Cancer Prevention, Cancer Center and M Sklodowska-Curie Institute of Oncology, Warsaw, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.affiliation: Department of Epidemiology and Public Health, Yale Cancer Center, Yale School of Public Health, New Haven, Connecticut, United States of America.
authors.forename: Lingeng
authors.initials: L
authors.lastname: Lu
authors.affiliation: H. Lee Moffitt Cancer Centre, Tampa, Florida, United States of America.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Magliocco
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: Department of Epidemiology and Public Health, Yale Cancer Center, Yale School of Public Health, New Haven, Connecticut, United States of America.
authors.forename: Harvey A
authors.initials: HA
authors.lastname: Risch
authors.affiliation: Division of Epidemiology, Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.|Cancer Registry of Norway, Oslo, Norway.|Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Giske
authors.initials: G
authors.lastname: Ursin
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, United States of America.
authors.forename: Hannah P
authors.initials: HP
authors.lastname: Yang
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
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.|Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Immaculata
authors.initials: I
authors.lastname: De Vivo
mesh_terms: D000368:Aged; D015992:Body Mass Index; D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D044465:White People / Q000235:genetics