Association of Physical Activity with Colorectal Cancer Risk: Stratified Analyses in a Prospective Cohort

Background: Colorectal cancer (CRC) is a significant and rising health burden globally and in Korea. While physical activity (PA) reduces CRC risk, evidence remains limited, especially in the Korean population. Additionally, the protective effect of PA may be modified by individual characteristics and is unclear in combination with sedentary behavior (SB). This study aimed to evaluate the association between PA and CRC risk in Korean populations, exploring subgroup-specific effects and the combined effect of PA and SB. Methods: Korean Multi-Center Cancer Cohort included 20,631 participants from various regions. Of these subjects, 4,675 men completed a PA-related questionnaire at baseline. Hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC incidence risk were estimated using multivariable Cox proportional hazards models. Models were adjusted for age, cigarette smoking, educational level, alcohol drinking, and body mass index (BMI). Stratified analyses were performed by individual characteristics (e.g., age, BMI, and smoking status) to assess effect modification. The relationship was further assessed considering the joint effect of PA and SB. Results: Non-occupational PA (NOPA) level of 300-599 MET min/week was associated with a decreased risk of CRC (HR=0.14, 95% CI=0.04–0.61) compared to the inactive NOPA group. Stratified analyses revealed that NOPA level of 300-599 MET was linked to lowered CRC risk in age < 65 group, smokers and BMI < 25 group (HR=0.12, 95% CI=0.02–0.86; HR=0.08, 95% CI=0.01–0.60; HR=0.12, 95% CI=0.02–0.89, respectively). Additionally, combined analysis indicated that individuals with active NOPA and short SB had a significantly lower risk of CRC compared to those with inactive NOPA and prolonged SB (HR=0.25, 95% CI=0.08–0.83). Conclusions: This study indicates that NOPA of 300–599 MET min/week was associated with a reduced risk of CRC, particularly in younger individuals, smokers, and those with lower BMI. The protective effect was more evident when active NOPA was combined with short SB. These findings highlight PA as a modifiable factor in CRC prevention and the importance of incorporating individual characteristics into public health strategies.