Sex- and Smoking-Specific Association between Physical Activity and Digestive Cancer Risk.

BACKGROUND: This study examined whether suboptimal and excess levels of physical activity (PA) relate to the development of digestive tract cancers, and whether these relationships differ according to sex and smoking history. SUBJECTS/METHODS: We performed a population-based cohort analysis using records from a nationwide health examination and gastric cancer screening conducted in 2010 and followed up to 2017. Weekly frequency of moderate-intensity PA was stratified into four groups: inactive (0 days/week), light (1-2 days/week), active (3-5 days/week), and highly active (6-7 days/week). The relationship between PA frequency and digestive cancer was quantified via Cox proportional hazards regression, with results expressed as adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS: A total of 4.5 million adults were analyzed, of whom 271,247 received a new cancer diagnosis. Relative to light PA group, sedentary behavior was associated with higher risk of overall (aHR 1.02; 95% CI 1.01-1.03), gastric (aHR 1.04; 95% CI 1.01-1.07), liver (aHR 1.10; 95% CI 1.06-1.15), gallbladder (aHR 1.13; 95% CI 1.03-1.24), and colorectal cancers (aHR 1.05; 95% CI 1.02-1.08). Similarly, the highest-frequency PA group showed elevated risks for overall (aHR 1.06; 95% CI 1.04-1.08), gastric (aHR 1.09; 95% CI 1.04-1.14), and colorectal cancers (aHR 1.05; 95% CI 1.00-1.11). Sex and smoking modified these effects: among men, both sedentary behavior and high-frequency PA were associated with greater risks of overall and gastric cancers, whereas sedentary behavior was linked to colorectal cancer risk in men and gallbladder cancer risk in women. In never-smokers, both extremes of PA frequency were associated with elevated risks of gallbladder and gastric cancers. CONCLUSION: A non-linear, U-shaped pattern of association was observed between PA frequency and digestive cancer risk. These associations were most pronounced in men and in individuals who had never smoked. However, most observed effect sizes were modest, and the findings should be interpreted cautiously given the potential for residual confounding and exposure misclassification.