Physical Activity, Tumor PTGS2 Expression, and Colorectal Cancer Survival: A Molecular Pathological Epidemiology (MPE) Approach

Purpose: Evidence suggests that energy balance in tumor microenvironment may influence systemic inflammatory status and cancer progression through its effect on prostaglandin biosynthesis. We examined whether the physical activity after diagnosis of colorectal cancer was associated with improved survival in PTGS2-positive colorectal cancer. Methods: Utilizing 605 stage I–III colon and rectal cancers in two prospective cohort studies, we assessed patient survival according to physical activity and tumor PTGS2 status. Cox proportional hazards regression was used to calculate multivariate hazard ratio (HR), adjusting for clinical and other tumor features (including microsatellite instability and BRAF and KRAS mutations). Results: Among patients with PTGS2-positive cancer, compared with the least active first quartile, the multivariate HRs were 0.30 (95% confidence interval [CI], 0.14–0.62) for the second quartile, 0.38 (95% CI, 0.20–0.71) for the third quartile, and 0.18 (95% CI, 0.08–0.41) for the fourth quartile of increasing physical activity (P = 0.0002 for trend). In contrast, among patients with PTGS2-negative cancer, physical activity level was not significantly associated with colorectal cancer-specific survival (P = 0.84 for trend). We observed significant interaction between physical activity and tumor PTGS2 status (P = 0.024 for interaction). Conclusion: Post-diagnosis physical activity was associated with better survival among patients with PTGS2-positive colorectal cancer. This finding from molecular pathological epidemiology (MPE) suggests that PTGS2 may be a tumor biomarker that may predict stronger benefit from exercise in colorectal cancer patients.