Body mass index and molecular subtypes of colorectal cancer.
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
- Population Science Department, American Cancer Society (ACS), Atlanta, GA, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
- Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, UK.
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
- Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, Australia.
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, MO, USA.
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
- Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- Department of Pathology, Emory University, Atlanta, GA, USA.
- Division of Laboratory Genetics, Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA.
- Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.
- Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA.
- Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden.
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
- University of Hawaii Cancer Center, Epidemiology Program, Honolulu, HI, USA.
- Mayo Clinic, Rochester, MN, USA.
- Program in Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
- Unit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain.
- Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
- Department of Clinical Pathology, The University of Melbourne, Melbourne, VIC, Australia.
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- Departments of Cancer Biology and Genetics and Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
- Ontario Institute for Cancer Research, Toronto, ON, Canada.
- Memorial University of Newfoundland, Discipline of Genetics, St. John's, NL, Canada.
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
BACKGROUND: Obesity is an established risk factor for colorectal cancer (CRC), but the evidence for the association is inconsistent across molecular subtypes of the disease.
METHODS: We pooled data on body mass index (BMI), tumor microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, and Jass classification types for 11 872 CRC cases and 11 013 controls from 11 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for covariables.
RESULTS: Higher BMI was associated with increased CRC risk (OR per 5 kg/m2 = 1.18, 95% CI = 1.15 to 1.22). The positive association was stronger for men than women but similar across tumor subtypes defined by individual molecular markers. In analyses by Jass type, higher BMI was associated with elevated CRC risk for types 1-4 cases but not for type 5 CRC cases (considered familial-like/Lynch syndrome microsatellite instability-H, CpG island methylator phenotype-low or negative, BRAF-wild type, KRAS-wild type, OR = 1.04, 95% CI = 0.90 to 1.20). This pattern of associations for BMI and Jass types was consistent by sex and design of contributing studies (cohort or case-control).
CONCLUSIONS: In contrast to previous reports with fewer study participants, we found limited evidence of heterogeneity for the association between BMI and CRC risk according to molecular subtype, suggesting that obesity influences nearly all major pathways involved in colorectal carcinogenesis. The null association observed for the Jass type 5 suggests that BMI is not a risk factor for the development of CRC for individuals with Lynch syndrome.