The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women
Lurie, Galina , Gaudet, Mia , Spurdle, Amanda , Carney, Michael , Wilkens, Lynne , Yang, Hannah , Weiss, Noel , Webb, Penelope , Thompson, Pamela , Terada, Keith , Setiawan, Veronica , Rebbeck, Timothy , Prescott, Jennifer , Orlow, Irene , O'Mara, Tracy, Olson, Sara , Narod, Steven , Matsuno, Rayna , Lissowska, Jola , Liang, Xiaolin , Levine, Douglas , Le Marchand, Loic , Kolonel, Laurence , Henderson, Brian , Garcia-Closas, Montserrat , Doherty, Jennifer , De Vivo, Immaculata , Chen, Chu , Brinton, Louise , Akbari, Mohammad , & Goodman, Marc (2011) The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women. PLoS ONE, 6(2), pp. 1-8.
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.
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|Item Type:||Journal Article|
|Subjects:||Australian and New Zealand Standard Research Classification > AGRICULTURAL AND VETERINARY SCIENCES (070000)|
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000)
|Divisions:||Current > QUT Faculties and Divisions > Faculty of Health|
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2011 the authors|
|Copyright Statement:||This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose|
|Deposited On:||19 Jul 2012 16:31|
|Last Modified:||09 Apr 2014 22:21|
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