Journal
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
Volume 24, Issue 7, Pages 1024-1031Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1055-9965.EPI-14-1309
Keywords
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Funding
- Mayo Clinic Cooperative Family Registry for Colon Cancer Studies [U01/U24 CA074800]
- University of Hawaii Colorectal Cancer Family Registry [U01/U24 CA074806]
- Familial Colorectal Neoplasia Collaborative Group [U01 CA074799]
- NIH [R01 CA151993, R01 CA137178, P01 CA53996, R01 AG14358, 1U54CA155626-01, R25 CA094880, R01 DK062370, UM1 CA167551, R01 CA48998, P01 CA 055075, UM1 CA167552, R01 137178, R01 CA 151993, P50 CA 127003, U01 CA074783, U01 HG004446, R01 CA076366, K05 CA154337]
- National Cancer Institute, NIH, U.S. Department of Health and Human Services [U01 CA137088, R01 CA059045]
- National Cancer Institute, NIH [U01 CA122839, R01 CA143237]
- NIH: Australasian Colorectal Cancer Family Registry [U01 CA074778, U01/U24 CA097735]
- Ontario Registry for Studies of Familial Colorectal Cancer [U01/U24 CA074783]
- Seattle Colorectal Cancer Family Registry [U01/U24 CA074794]
- German Research Council (Deutsche Forschungsgemeinschaft) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]
- German Federal Ministry of Education and Research [01KH0404, 01ER0814]
- NHS by the NIH [R01 CA151993, R01 CA137178, P50 CA 127003, P01 CA 087969]
- PHS by the NIH [R01 CA042182]
- Ontario Research Fund
- Canadian Institutes of Health Research
- Ontario Institute for Cancer Research
- Ontario Ministry of Research and Innovation
- Intramural Research Program of the Division of Cancer Epidemiology and Genetics
- Division of Cancer Prevention, National Cancer Institute, NIH, DHHS
- NIH, Genes, Environment and Health Initiative (GEI) [Z01 CP 010200]
- NIH GEI [U01 HG 004438]
- National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]
- Lundbeck Foundation [R190-2014-3904] Funding Source: researchfish
- NNF Center for Basic Metabolic Research [Pers Group] Funding Source: researchfish
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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: Weused 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. Impact: Overall, conventional epidemiologic and Mendelian randomization studies suggest a strong association between obesity and the risk of colorectal cancer. (C) 2015 AACR.
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