title: Mendelian Randomization Study of Body Mass Index and Colorectal Cancer Risk.
abstract: BACKGROUND
  High body mass index (BMI) is consistently linked to increased risk of colorectal cancer for men, whereas the association is less clear for women. As risk estimates from observational studies may be biased and/or confounded, we conducted a Mendelian randomization study to estimate the causal association between BMI and colorectal cancer.
  
  
  METHODS
  We used data from 10,226 colorectal cancer cases and 10,286 controls of European ancestry. The Mendelian randomization analysis used a weighted genetic risk score, derived from 77 genome-wide association study-identified variants associated with higher BMI, as an instrumental variable (IV). We compared the IV odds ratio (IV-OR) with the OR obtained using a conventional covariate-adjusted analysis.
  
  
  RESULTS
  Individuals carrying greater numbers of BMI-increasing alleles had higher colorectal cancer risk [per weighted allele OR, 1.31; 95% confidence interval (CI), 1.10-1.57]. Our IV estimation results support the hypothesis that genetically influenced BMI is directly associated with risk for colorectal cancer (IV-OR per 5 kg/m(2), 1.50; 95% CI, 1.13-2.01). In the sex-specific IV analyses higher BMI was associated with higher risk of colorectal cancer among women (IV-OR per 5 kg/m(2), 1.82; 95% CI, 1.26-2.61). For men, genetically influenced BMI was not associated with colorectal cancer (IV-OR per 5 kg/m(2), 1.18; 95% CI, 0.73-1.92).
  
  
  CONCLUSIONS
  High BMI was associated with increased colorectal cancer risk for women. Whether abdominal obesity, rather than overall obesity, is a more important risk factor for men requires further investigation.
  
  
  CONCLUSIONS
  Overall, conventional epidemiologic and Mendelian randomization studies suggest a strong association between obesity and the risk of colorectal cancer.
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Medicine and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas. aaron.thrift@bcm.edu.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Thrift
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Jian
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authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington.
authors.forename: Ulrike
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authors.lastname: Peters
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Jenny
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authors.lastname: Chang-Claude
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Anja
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authors.lastname: Rudolph
authors.affiliation: Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
authors.affiliation: Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.
authors.forename: Adam E
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authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan.
authors.forename: Bratati
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authors.lastname: Kahali
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Anne E
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authors.lastname: Justice
authors.affiliation: Divisions of Endocrinology and Genetics and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts. Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts. Department of Genetics, Harvard Medical School, Boston, Massachusetts. Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Tune H
authors.initials: TH
authors.lastname: Pers
authors.affiliation: Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Steven
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authors.lastname: Gallinger
authors.affiliation: Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, New York.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.affiliation: Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
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authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, California.
authors.forename: Bette J
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authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Shuji
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authors.lastname: Ogino
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Stephen J
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authors.lastname: Chanock
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
authors.forename: Graham
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authors.lastname: Casey
authors.affiliation: Department of Medicine, Division of Oncology, Stanford University, Stanford, California.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Mengmeng
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authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
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authors.lastname: Harrison
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Mark
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authors.lastname: Thornquist
authors.affiliation: Translational Genomics Research Institute, Phoenix, Arizona.
authors.forename: David J
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authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
authors.forename: Loïc
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authors.lastname: Le Marchand
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona.
authors.forename: Noralane M
authors.initials: NM
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authors.affiliation: Division of Cancer Control and Population Sciences, National Cancer Institute, NIH, Bethesda, Maryland.
authors.forename: Daniela
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authors.lastname: Seminara
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.
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authors.lastname: Song
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.
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authors.affiliation: Departments of Laboratory Medicine and Pathology and Laboratory Genetics, Mayo Clinic, Rochester, Minnesota.
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authors.affiliation: Prevention and Cancer Control, Cancer Care Ontario, Toronto, Canada.
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authors.affiliation: Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Aung Ko
authors.initials: AK
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authors.affiliation: Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
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authors.lastname: Jenkins
authors.affiliation: Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
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authors.affiliation: Population Sciences Huntsman Cancer Institute, Salt Lake City, Utah.
authors.forename: Cornelia M
authors.initials: CM
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authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington. Centre for Public Health Research, Massey University, Wellington, New Zealand.
authors.forename: John D
authors.initials: JD
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authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington.
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Michael
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authors.lastname: Hoffmeister
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. German Cancer Consortium (DKTK), Heidelberg, Germany.
authors.forename: Hermann
authors.initials: H
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authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington.
authors.forename: Emily
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authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Department of Biostatistics, School of Public Health, University of Washington, Seattle, Washington.
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mesh_terms: D015992:Body Mass Index; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D005060:Europe / Q000453:epidemiology; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis / Q000379:methods*; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D016017:Odds Ratio; D012307:Risk Factors