Physical activity, genetic susceptibility, and risk of colorectal cancer in type 2 diabetes: a large population-based cohort study

It is crucial to identify modifiable preventive measures to mitigate the risk of colorectal cancer (CRC) among patients with type 2 diabetes (T2D), a high-risk group for CRC. We conducted a study to investigate the potential association between various levels of physical activity (PA) and the incidence of CRC, taking account of genetic susceptibility, in a T2D population cohort. The study was based on UK Biobank (UKB) data on persons diagnosed with T2D; the participants were tracked until 2022. Hazard ratios (HR) and 95% confidence intervals (95% CI) for CRC were calculated using Cox regression models. The 33 733 patients with T2D were followed up for a median of 13.62 years. During this time, 551 patients were diagnosed with CRC. Compared with low PA, the multivariable adjusted HR for CRC among T2D patients was 0.81 (95% CI [0.66; 0.98]) and 0.74 (95% CI [0.58; 0.94]) in the groups with moderate and high PA, respectively. In right colon cancer, moderate and high levels of PA were associated with 31% (HR 0.69; 95% CI [0.51; 0.93]) and 42% (HR 0.58; 95% CI [0.40: 0.85]) reductions in the risk of CRC. High PA (HR 0.54; 95% CI, 0.35-0.84) was associated with a lower risk of CRC even in patients with a high polygenic risk score (PRS). Persons with low PRS and high PA had the lowest risk of CRC. Our study suggests that moderate to high PA helps to reduce the risk of CRC in T2D patients and that joint consideration of PA level and PRS could provide valuable insights for personalized strategies to prevent CRC.