The dose-response effect of aerobic exercise on inflammation in colon cancer survivors
Justin C. Brown, Stephanie L. E. Compton, Jeffrey A. Meyerhardt, Guillaume Spielmann, Shengping Yang
Abstract
Background: Physical activity after surgical resection for colon cancer is associated with significantly longer disease-free survival. Inflammation is hypothesized to mediate the association between physical activity and disease-free survival in colon cancer. Methods: In this exploratory analysis of a randomized dose-response trial, 39 colon cancer survivors who completed standard therapy were stratified by cancer stage and randomized in a 1:1:1 ratio to one of three treatment groups for 24 weeks of usual-care control, 150 min/wk of moderate-intensity aerobic exercise (low-dose), or 300 min/wk of moderate-intensity aerobic exercise (high-dose). Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL6), and soluble tumor necrosis factor-alpha receptor 2 (sTNFαR2). Mixed models for repeated measures were used to test the hypothesis that exercise was associated with dose-response reductions in inflammation; exploratory analyses examined treatment effects by cancer stage. Results: In the overall population, aerobic exercise was not associated with dose-response reductions in hs-CRP, IL6, or sTNFαR2. Cancer stage modified the association between randomized group and hs-CRP (P=0.022) and IL6 (P<0.001) but not sTNFαR2 (P=0.39). In stage I-II disease, compared to control, exercise was not associated with inflammation outcomes. In stage III disease, compared to control, low-dose exercise reduced hs-CRP: -35.4% (95% CI: -70.1, -0.7) and IL6: -29.6% (95% CI: -58.4, -0.8) but not sTNFαR2: 2.7% (95% CI: sTNFαR2: -15.7, 21.1); high-dose exercise was not associated with inflammation outcomes in stage III disease. Conclusion: This exploratory analysis offers preliminary data to support the hypothesis that inflammation may mediate the association between physical activity and disease-free survival in colon cancer. Clinical trial registration: clinicaltrials.gov, identifier NCT02250053.