title: Common variants in the obesity-associated genes FTO and MC4R are not associated with risk of colorectal cancer.
abstract: 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.
  
  
  
  In the discovery stage, we tested associations of 677 FTO and 323 MC4R single nucleotide polymorphisms (SNPs) 100kb upstream and 300kb 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).
  
  
  
  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.
  
  
  
  We found no evidence that individual variants in or near the obesity-related genes FTO and MC4R are associated with risk of colorectal cancer.
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
authors.forename: Baiyu
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Medicine and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Thrift
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Figueiredo
authors.affiliation: Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Fredrick R
authors.initials: FR
authors.lastname: Schumacher
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: David V
authors.initials: DV
authors.lastname: Conti
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Aung Ko
authors.initials: AK
authors.lastname: Win
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Limburg
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Preventive Oncology and National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hoffmeister
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Canada; Ontario Institute for Cancer Research, Toronto, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Canada.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hudson
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
authors.forename: Loïc Le
authors.initials: LL
authors.lastname: Marchand
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.affiliation: Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT, USA.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: White
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Peters
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA. Electronic address: Peter.Campbell@cancer.org.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Campbell
mesh_terms: D000368:Aged; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*; D012307:Risk Factors
chemical_list: D044105:Receptor, Melanocortin, Type 4; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human
keywords: Case-control study; Colorectal cancer; Genetic variants; Obesity