Long-term running and risk of colorectal adenoma and cancer

Introduction: Although physical activity is associated with lower risk of colorectal cancer, it was hypothesized that high levels of long-distance running may induce gastrointestinal ischemia and injury, raising concern about potential increased risk of colorectal carcinogenesis. Currently only a small cross-sectional study of 100 participants suggested intensive long-distance running is a risk factor for advanced colon adenomas. No large prospective study has comprehensively evaluated long-term running in relation to risk of colorectal adenoma and cancer. Methods: We used data from three prospective cohorts: Health Professionals Follow-up Study, Nurses' Health Study (NHS), and NHSII. Running was assessed with biennial validated questionnaires and calculated as cumulative average over the past 8-year period to reflect long-term patterns. Colorectal adenoma risk was evaluated among 160,367 participants with at least one lower gastrointestinal endoscopy during follow-up with logistic regression models accounting for repeated observations. Colorectal cancer risk was analyzed with Cox proportional hazard models among 238,491 participants followed up to 32 years. Multivariable models were adjusted for potential confounders and total physical activity other than running. We also examined associations between running with resting heart rate and cardiometabolic biomarkers. Results: We documented 12,426 conventional adenomas, 11,251 serrated polyps, and 3583 colorectal cancers during the follow-up period. Running was inversely associated with risk of conventional adenoma and serrated polyps. For high-risk adenoma, compared to participants who reported no running, the ORs (95% CIs) across >0-<1, 1-<2, 2-<3, 3-<4, and ≥4 h/week of running were 0.86 (0.76-0.98), 0.75 (0.55-1.00), 0.83 (0.56-1.23), 0.94 (0.52-1.66), and 0.51 (0.29-0.91), respectively. For colorectal cancer, compared to no running, the HRs (95% CIs) were 0.86 (0.76-0.97) for >0-<1 h/week, 0.60 (0.41-0.87) for 1-<2 h/week, and 0.81 (0.58-1.12) for ≥2 h/week. Results remained similar when further adjusted for body mass index. Biomarker analysis showed higher levels of running were associated with significant lower resting heart rate, lower inflammation status (lower CRP and IL-6), better insulinemic (lower C-peptide) and lipid profile (higher HDL-cholesterol and lower triglycerides), providing biologic support of our assessment of running. Conclusion: In three large cohorts, long-term running was not associated with an increased risk of colorectal adenoma, serrated polyps, or colorectal cancer. Moderate running levels (approximately up to 2 h/week) were associated with lower risk of colorectal cancer and levels ≥4 h/week were associated with a lower risk of high-risk adenoma. These findings provide reassurance that habitual running, at levels up to at least 4 h/week, is safe and potentially beneficial with respect to colorectal neoplasia risk.