OBJECTIVES: The prevalence of colorectal cancer (CRC) is higher among people with type 2 diabetes mellitus (T2DM) than among people without diabetes. Furthermore, men are at higher risk for developing CRC than women in the general population and also subsite-specific risks differ by sex. The aim was to evaluate the impact of T2DM on these associations.

METHODS: People with T2DM were selected from the PHARMO Database Network and matched (1:4) to diabetes free-controls. Incidence rates of CRC were compared using Cox proportional hazards modelling. Hazard ratios (HR) and 95% confidence intervals (CIs) were determined per sex and subsite of CRC and adjusted for age and socioeconomic status. The ratio of distal versus proximal colon cancer was calculated for people with T2DM and controls per sex and stratified by age.

RESULTS: Over 50,000 people with T2DM were matched to >215,000 diabetes free-controls. Mean follow-up time was almost 4 years for cases and 3.5-3.7 years for controls. Men and women with T2DM were 1.3 times more likely to develop CRC compared to controls. Compared to controls, men with T2DM were at higher risk to develop distal colon cancer (HR (95% CI): 1.42 (1.08-1.88)) than women with T2DM (HR (95% CI): 0.86 (0.55-1.35)). Women with T2DM were at higher risk to develop proximal colon cancer (HR (95% CI): 1.58 (1.13-2.19)) than men with T2DM (HR (95% CI): 1.20 (0.87-1.65)). For rectal cancer, no statistically significant risk was observed for both men and women. These findings remained after applying a 1-year lag-period to account for detection bias. Furthermore, women with T2DM aged ≥70 years were more likely to develop proximal rather than distal colon cancer.

CONCLUSIONS: Sex-specific screening strategies and prevention protocols should be considered for people with T2DM. More tailored screening strategies may optimize the effectiveness of CRC screening in terms of reducing incidence and mortality.