title: The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women.
abstract: Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2). This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively). In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR)  = 1.17; 95% confidence interval (CI): 1.03-1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI), suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91-1.06; p = 0.68). FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis.
authors.affiliation: Cancer Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii, United States of America.
authors.forename: Galina
authors.initials: G
authors.lastname: Lurie
authors.forename: Mia M
authors.initials: MM
authors.lastname: Gaudet
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Spurdle
authors.forename: Michael E
authors.initials: ME
authors.lastname: Carney
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Wilkens
authors.forename: Hannah P
authors.initials: HP
authors.lastname: Yang
authors.forename: Noel S
authors.initials: NS
authors.lastname: Weiss
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Webb
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Thompson
authors.forename: Keith
authors.initials: K
authors.lastname: Terada
authors.forename: Veronica Wendy
authors.initials: VW
authors.lastname: Setiawan
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
authors.forename: Jennifer
authors.initials: J
authors.lastname: Prescott
authors.forename: Irene
authors.initials: I
authors.lastname: Orlow
authors.forename: Tracy
authors.initials: T
authors.lastname: O'Mara
authors.forename: Sara H
authors.initials: SH
authors.lastname: Olson
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.forename: Rayna K
authors.initials: RK
authors.lastname: Matsuno
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liang
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Levine
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Closas
authors.forename: Jennifer Anne
authors.initials: JA
authors.lastname: Doherty
authors.forename: Immaculata
authors.initials: I
authors.lastname: De Vivo
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Akbari
authors.forename: Marc T
authors.initials: MT
authors.lastname: Goodman
mesh_terms: D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: C470072:MC4R protein, human; D011506:Proteins; D044105:Receptor, Melanocortin, Type 4; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human