Background: Diabetes is associated with a modest increased risk of colorectal cancer (CRC). Evidence also indicates that high endogenous insulin and glucose levels are associated with increased risk of CRC. However, few studies have evaluated whether exogenous insulin, used to treat diabetes, is associated with risk of CRC, and one of these studies reported strongly increased risk among diabetics who had used insulin. Further, few studies have examined the association between diabetes and risk of CRC by gender, tumor phenotype (e.g., sub-site, stage) and other factors, that may be relevant to the etiology of CRC.

Methods: The CPS II Nutrition Cohort is a prospective study of cancer incidence including approximately 184,000 U.S. adults aged 50 to 75 at enrollment in 1992-93. At enrollment, participants completed a detailed self-administered questionnaire that included information on demographic, medical, lifestyle, and dietary factors. The questionnaire asked if a participant had been diagnosed by a physician with diabetes mellitus and if the participant was taking insulin to treat the disease. Follow-up questionnaires were sent to cohort members in 1997, and every two years thereafter to update exposure information, including diabetes and insulin-use, and to learn of incident cancers. Colorectal cancer cases in the current study were identified by linkage with the National Death Index (NDI) or by self-reports, subsequently verified by medical record abstraction or linkage with state cancer registries.

Results: After exclusions, 73,328 men and 81,670 women remained in the final analytic cohort, of whom 1,444 men and 1,154 women were diagnosed with colon or rectal cancer between enrollment and the end of follow-up in 2007. Among female participants, diabetes and insulin-use were not associated with incident colorectal cancer overall (Relative Risk (RR): 0.98; 95% Confidence Interval (CI): 0.79-1.22 and RR: 0.92; 95% CI: 0.61-1.40, respectively) or when stratified by tumor sub-site in the colon or rectum, stage of disease, or fatality. Among male participants, both diabetes and insulin-use were associated with modestly increased risk of incident colorectal cancer (RR: 1.25; 95% CI: 1.08-1.46 and RR: 1.35; 95% CI: 1.02-1.78, respectively). There were no clear differences in associations with diabetes by subsite or stage. Duration of diabetes was linearly associated with CRC risk among men (p-trend: 0.0002), but not women. Duration of insulin-use was not linearly associated with CRC risk in men or women.

Conclusions: Our results from a large U.S. prospective study confirm a modest association between diabetes and colorectal cancer risk among men but not among women. Reasons for these differences are unclear but might be due to sex-differences in hormones or better glucose control among women than men. Our results also suggest that exogenous insulin-use is unlikely to substantially increase risk of colorectal cancer among diabetics.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1841.