Increased Risk of Colon Cancer in Men in the Pre-Diabetes Phase

Background: Historically, studies exploring the association between type 2 diabetes mellitus (DM) and cancer lack accurate definition of date of DM onset, limiting temporal analyses. We examined the temporal relationship between colon cancer risk and DM using an electronic algorithm and clinical, administrative, and laboratory data to pinpoint date of DM onset. Methods: Subjects diagnosed with DM (N = 11,236) between January 1, 1995 and December 31, 2009 were identified and matched at a 5:1 ratio with 54 365 non-diabetic subjects by age, gender, smoking history, residence, and diagnosis reference date. Colon cancer incidence relative to the reference date was used to develop Cox regression models adjusted for matching variables, body mass index, insurance status, and comorbidities. Primary outcomes measures included hazard ratio (HR) and number needed to be exposed for one additional person to be harmed (NNEH). Results: The adjusted HR for colon cancer in men before DM onset was 1.28 (95% CI 1.04-1.58, P = 0.0223) and the NNEH decreased with time, reaching 263 at DM onset. No such difference was observed in women. After DM onset, DM did not appear to alter colon cancer risk in either gender. Conclusions: Colon cancer risk is increased in diabetic men, but not women, before DM onset. DM did not alter colon cancer risk in men or women after clinical onset. In pre-diabetic men, colon cancer risk increased as time to DM onset decreased, suggesting that the effects of the pre-diabetes phase on colon cancer risk in men are cumulative.