Abstract 3725: Long-term leisure-time physical activity and digestive system cancer risk and mortality

Abstract Introduction: Accumulating evidence indicates physical activity (PA) protects against digestive system cancer (DSC) risk. However, less is clear about its optimal amount, intensity, joint association with sedentary behavior, or its role in DSC mortality. Methods: A total of 231, 067 adults from 3 prospective US cohorts (Health Professionals Follow-up Study, 1988-2020; Nurses’ Health Study [NHS], 1988-2020; NHS II, 1991-2021) were analyzed. Leisure-time PA was assessed biennially via validated questionnaires and expressed in MET-h/week. Time spent sitting watching TV, a widely used surrogate of sedentary behavior, was assessed biennially. DSC encompassed the digestive tract (mouth, throat, esophagus, stomach, small intestine, colon and rectum) and accessory organs (pancreas, gallbladder, and liver). Results: Over up to 32 years of follow-up, we documented 6537 incident DSC and 3789 DSC deaths. Higher PA levels were associated with lower DSC risk (≥45 vs. <3 MET-h/week: HR [95% CI], 0.82 [0.74-0.92]; P-trend<0.001) and mortality (0.72 [0.62-0.84], P-trend<0.001). The inverse association was evident for both digestive tract and digestive accessory organ cancers. The maximum benefit appears to be reached at approximately 50 MET-hours/week for DSC risk (P non-linearity=0.01) and mortality (P non-linearity<0.001). Moderate and vigorous PA was independently associated with lower DSC risk and mortality. Consistently meeting the PA guidelines was further associated with lower risk of DSC. Participants who were highly active and less sedentary had a 22% lower DSC risk (95% CI, 0.69-0.87) than those who were highly sedentary and less active. Conclusion: Higher PA, whether moderate or vigorous, was associated with lower DSC risk and mortality. The optimal benefit was observed at approximately 50 MET-hours/week of total PA. Being consistently physically active may further reduce DSC risk. Increasing PA and reducing sedentariness may be strategies for preventing DSC risk and mortality. Citation Format: Yiwen Zhang, Edward L. Giovannucci. Long-term leisure-time physical activity and digestive system cancer risk and mortality [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3725.