Case-control study of overweight, obesity, and colorectal cancer risk, overall and by tumor microsatellite instability status

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. ThibodeauNoralane M. Lindor, Paul J. Limburg, María Elena Martínez

Research output: Contribution to journalArticlepeer-review

140 Scopus citations

Abstract

Background Being overweight or obese is an established risk factor for colorectal cancer, more so for men than for women. Approximately 10%-20% of colorectal tumors display microsatellite instability (MSI), defined as the expansion or contraction of small repeated sequences in the DNA of tumor tissue relative to nearby normal tissue. We evaluated associations between overweight or obesity and colorectal cancer risk, overall and by tumor MSI status.Methods The study included 1794 case subjects with incident colorectal cancer who were identified through population-based cancer registries and 2684 of their unaffected sex-matched siblings as control subjects. Recent body mass index (BMI), BMI at age 20 years, and adult weight change were derived from self-reports of height and weight. Tumor MSI status, assessed at as many as 10 markers, was obtained for 69.7% of the case subjects and classified as microsatellite (MS)-stable (0% of markers unstable; n = 913), MSI-low (>0% but <30% of markers unstable; n = 149), or MSI-high (≥30% of markers unstable; n = 188). Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). All statistical tests were two-sided.Results Recent BMI, modeled in 5 kg/m 2 increments, was positively associated with risk of colorectal cancer for men and women combined (OR = 1.24; 95% CI = 1.15 to 1.34), for women only (OR = 1.20; 95% CI = 1.10 to 1.32), and for men only (OR = 1.30; 95% CI = 1.15 to 1.47). There was no interaction with sex (P =. 22). Recent BMI, per 5 kg/m2, was positively associated with the risk of MS-stable (OR = 1.38; 95% CI = 1.24 to 1.54) and MSI-low (OR = 1.33; 95% CI = 1.04 to 1.72) colorectal tumors, but not with the risk of MSI-high tumors (OR = 1.05; 95% CI = 0.84 to 1.31).Conclusion The increased risk of colorectal cancer associated with a high BMI might be largely restricted to tumors that display the more common MS-stable phenotype, suggesting further that colorectal cancer etiology differs by tumor MSI status.

Original languageEnglish (US)
Pages (from-to)391-400
Number of pages10
JournalJournal of the National Cancer Institute
Volume102
Issue number6
DOIs
StatePublished - Mar 2010

Bibliographical note

Funding Information:
National Cancer Institute, National Institutes of Health, under RFA CA-95-011 and through cooperative agreements with the Australasian Colorectal Cancer Family Registry (U01 CA097735), the University of Southern California Familial Colorectal Neoplasia Collaborative Group (U01 CA074799), the Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01 CA074800), the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783), the Seattle Colorectal Cancer Family Registry (U01 CA074794), and the University of Hawaii Colorectal Cancer Family Registry (U01 CA074806). Data collection in Newfoundland and Labrador was funded by the Canadian Institutes of Health Research, (CRT-43821 and CRT-79845). Work at the Arizona Cancer Center is supported by the National Cancer Institute, National Institutes of Health (CA041108-19). P.T.C. was supported in part by a National Cancer Institute of Canada post-PhD Fellowship (No. 18735) and also supported in part by a National Institutes of Health Transdisciplinary Research on Energetics and Cancer Postdoctoral Fellowship (NCI U54 CA116847). E.T.J. is supported by a National Cancer Institute Career Development Award (1K07CA10629-01A1). J.C.F. was supported in part by a National Cancer Institute of Canada post-PhD Fellowship (No. 17602). J.N.P. was supported in part by the National Cancer Institute (T32 CA009142).

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