Physical activity reduces cancer risk by lowering chronic inflammation: a dual-cohort study in the Chinese population

The mainland of China accounts for 18.66% of the world’s population, 24.17% of global cancer new cases, and 26.44% cancer-related death worldwide in 2022, indicating cancer burden is extremely heavy in this region. It is of great significance to explore a cost-effective strategy for cancer prevention and control. Physical activity (PA) is expected to decrease the risks of cancer occurrence and cancer-related death. However, the effects of PA on cancer burden in China and the mechanisms by which PA prevents cancer remain to be elucidated because these data are current lacking. Here, a total of 522165 subjects from the China Kadoorie Biobank (CKB) and Shanghai cohort were invited to join in this study to reveal the associations of PA with the risks of cancer occurrence and cancer-related death and their underlying mechanisms by which PA decreases the burden of cancer. Circulating C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) were used to represent inflammation levels in the two cohorts, respectively. Demographic information was collected using a structured questionnaire. Healthy participants were defined as those without any chronic disease at baseline. Cox proportional hazard model was used to analyze factors that contribute to cancer occurrence and cancer-related mortality. It was found that the circulating levels of CRP and hs-CRP were significantly lower in the participants with PA that in those without PA in either entire study subjects or healthy participants at baselines. Compared to the participants with lower inflammation, those with higher inflammation had a higher risk of cancer occurrence, with a hazard ratio (HR) and 95% confidence interval (95% CI) of 1.252 and 1.031–1.520 in Shanghai cohort and 1.351 and 1.172–1.558 in CKB as well as a higher risk of cancer-related death, with a HR and 95% CI of 1.491 and 1.179–1.886 in Shanghai cohort and 1.428 and 1.203–1.696 in CKB. Restricted cubic spline (RCS) analysis demonstrated a significant non-linear positive correlation between the circulating levels of CRP/hs-CRP and the risks of cancer occurrence and cancer-related death. In Shanghai cohort, PA was significantly associated with a decreased risk of cancer mortality (log-rank P=0.020). In the CKB cohort, jogging was associated with a lower level of systemic inflammation, lower risk of cancer occurrence, and lower risk of cancer mortality than did other PA modalities. The study provides robust population-based evidence supporting the hypothesis that PA, particularly jogging, confers efficient protection against cancer occurrence and cancer-related mortality partly via lowering systemic low-grade inflammation, indicating that PA especially jogging is of public health significance for cancer prevention and control, which can be suggested as a useful public health strategy against cancer.