Common variants in the obesity-associated genes FTO and MC4R are not associated with risk of colorectal cancer

• Type of Material: Article
• Authors: Baiyu Yang, Emory University; Aaron P. Thrift, Baylor College of Medicine; Jane C. Figueiredo, University of Southern California; Mark A. Jenkins, University of Melbourne; Fredrick R. Schumacher, University of Southern California; David V. Conti, University of Southern California; Yi Lin, Fred Hutchinson Cancer Research Center; Aung Ko Win, University of Melbourne; Paul J. Limburg, Mayo Clinic; Sonja I. Berndt, National Cancer Institute; Hermann Brenner, German Cancer Research Center; Andrew T. Chan, Harvard Medical School; Jenny Chang-Claude, German Cancer Research Center; Michael Hoffmeister, German Cancer Research Center; Thomas J. Hudson, University of Toronto; Loic Le Marchand, University of Hawaii; Polly A. Newcomb, Fred Hutchinson Cancer Research Center; Martha L. Slattery, University of Utah; Emily White, Fred Hutchinson Cancer Research Center; Ulrike Peters, University of Washington; Graham Casey, University of Southern California; Peter Campbell, Emory University
• Language: English
• Date: 2016-10-01
• Publisher: Elsevier Science Ltd.
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.canep.2016.07.003
• Title of Journal or Parent Work: Cancer Epidemiology
• Volume: 44
• Start Page: 1
• End Page: 4
• Grant/Funding Information: None declared
• Keywords: Oncology; Obesity; Case-control study; Colorectal cancer; Genetic variants; Loci; Meta-analysis; Public, Environmental & Occupational Health; Life Sciences & Biomedicine; Science & Technology
• Research Categories: Biology, Genetics; Health Sciences, Occupational Health and Safety; Health Sciences, Oncology

Abstract

Background: Obesity is a convincing risk factor for colorectal cancer. Genetic variants in or near FTO and MC4R are consistently associated with body mass index and other body size measures, but whether they are also associated with colorectal cancer risk is unclear. Methods: In the discovery stage, we tested associations of 677 FTO and 323 MC4R single nucleotide polymorphisms (SNPs) 100 kb upstream and 300 kb downstream from each respective locus with risk of colorectal cancer in data from the Colon Cancer Family Registry (CCFR: 1960 cases; 1777 controls). Next, all SNPs that were nominally statistically significant (p < 0.05) in the discovery stage were included in replication analyses in data from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO: 9716 cases; 9844 controls). Results: In the discovery stage, 43 FTO variants and 18 MC4R variants were associated with colorectal cancer risk (p < 0.05). No SNPs remained statistically significant in the replication analysis after accounting for multiple comparisons. Conclusion: We found no evidence that individual variants in or near the obesity-related genes FTO and MC4R are associated with risk of colorectal cancer.