Baiyu Yang1, Aaron P Thrift2, Jane C Figueiredo3, Mark A Jenkins4, Fredrick R Schumacher3, David V Conti3, Yi Lin5, Aung Ko Win4, Paul J Limburg6, Sonja I Berndt7, Hermann Brenner8, Andrew T Chan9, Jenny Chang-Claude10, Michael Hoffmeister11, Thomas J Hudson12, Loïc Le Marchand13, Polly A Newcomb14, Martha L Slattery15, Emily White14, Ulrike Peters14, Graham Casey3, Peter T Campbell16. 1. Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA. 2. Department of Medicine and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA. 3. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. 4. Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia. 5. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 6. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. 7. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. 8. 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. 9. 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. 10. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 11. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. 12. 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. 13. Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA. 14. 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. 15. Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT, USA. 16. Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA. Electronic address: Peter.Campbell@cancer.org.
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) 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). 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.
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) 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). 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.
Authors: Aaron P Thrift; Jian Gong; Ulrike Peters; Jenny Chang-Claude; Anja Rudolph; Martha L Slattery; Andrew T Chan; Adam E Locke; Bratati Kahali; Anne E Justice; Tune H Pers; Steven Gallinger; Richard B Hayes; John A Baron; Bette J Caan; Shuji Ogino; Sonja I Berndt; Stephen J Chanock; Graham Casey; Robert W Haile; Mengmeng Du; Tabitha A Harrison; Mark Thornquist; David J Duggan; Loïc Le Marchand; Noralane M Lindor; Daniela Seminara; Mingyang Song; Kana Wu; Stephen N Thibodeau; Michelle Cotterchio; Aung Ko Win; Mark A Jenkins; John L Hopper; Cornelia M Ulrich; John D Potter; Polly A Newcomb; Michael Hoffmeister; Hermann Brenner; Emily White; Li Hsu; Peter T Campbell Journal: Cancer Epidemiol Biomarkers Prev Date: 2015-05-14 Impact factor: 4.254
Authors: Peter T Campbell; Elizabeth T Jacobs; Cornelia M Ulrich; Jane C Figueiredo; Jenny N Poynter; John R McLaughlin; Robert W Haile; Eric J Jacobs; Polly A Newcomb; John D Potter; Loïc Le Marchand; Roger C Green; Patrick Parfrey; H Banfield Younghusband; Michelle Cotterchio; Steven Gallinger; Mark A Jenkins; John L Hopper; John A Baron; Stephen N Thibodeau; Noralane M Lindor; Paul J Limburg; María Elena Martínez Journal: J Natl Cancer Inst Date: 2010-03-05 Impact factor: 13.506
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Authors: Polly A Newcomb; John Baron; Michelle Cotterchio; Steve Gallinger; John Grove; Robert Haile; David Hall; John L Hopper; Jeremy Jass; Loïc Le Marchand; Paul Limburg; Noralane Lindor; John D Potter; Allyson S Templeton; Steve Thibodeau; Daniela Seminara Journal: Cancer Epidemiol Biomarkers Prev Date: 2007-11-02 Impact factor: 4.254
Authors: A Tenesa; H Campbell; E Theodoratou; L Dunlop; R Cetnarskyj; S M Farrington; M G Dunlop Journal: Int J Obes (Lond) Date: 2008-12-09 Impact factor: 5.095
Authors: Ulrike Peters; Shuo Jiao; Fredrick R Schumacher; Carolyn M Hutter; Aaron K Aragaki; John A Baron; Sonja I Berndt; Stéphane Bézieau; Hermann Brenner; Katja Butterbach; Bette J Caan; Peter T Campbell; Christopher S Carlson; Graham Casey; Andrew T Chan; Jenny Chang-Claude; Stephen J Chanock; Lin S Chen; Gerhard A Coetzee; Simon G Coetzee; David V Conti; Keith R Curtis; David Duggan; Todd Edwards; Charles S Fuchs; Steven Gallinger; Edward L Giovannucci; Stephanie M Gogarten; Stephen B Gruber; Robert W Haile; Tabitha A Harrison; Richard B Hayes; Brian E Henderson; Michael Hoffmeister; John L Hopper; Thomas J Hudson; David J Hunter; Rebecca D Jackson; Sun Ha Jee; Mark A Jenkins; Wei-Hua Jia; Laurence N Kolonel; Charles Kooperberg; Sébastien Küry; Andrea Z Lacroix; Cathy C Laurie; Cecelia A Laurie; Loic Le Marchand; Mathieu Lemire; David Levine; Noralane M Lindor; Yan Liu; Jing Ma; Karen W Makar; Keitaro Matsuo; Polly A Newcomb; John D Potter; Ross L Prentice; Conghui Qu; Thomas Rohan; Stephanie A Rosse; Robert E Schoen; Daniela Seminara; Martha Shrubsole; Xiao-Ou Shu; Martha L Slattery; Darin Taverna; Stephen N Thibodeau; Cornelia M Ulrich; Emily White; Yongbing Xiang; Brent W Zanke; Yi-Xin Zeng; Ben Zhang; Wei Zheng; Li Hsu Journal: Gastroenterology Date: 2012-12-22 Impact factor: 22.682
Authors: Sara Hägg; Andrea Ganna; Sander W Van Der Laan; Tonu Esko; Tune H Pers; Adam E Locke; Sonja I Berndt; Anne E Justice; Bratati Kahali; Marten A Siemelink; Gerard Pasterkamp; David P Strachan; Elizabeth K Speliotes; Kari E North; Ruth J F Loos; Joel N Hirschhorn; Yudi Pawitan; Erik Ingelsson Journal: Hum Mol Genet Date: 2015-09-16 Impact factor: 6.150