Physical Activity and Cancer Incidence and Mortality: Current Evidence and Biological Mechanisms

Objectives: There is strong evidence that not enough physical activity is among the most critical risk factors for cancer disease and premature mortality. The literature on the benefits of regular physical activity regarding cancer disease has grown in the last decades. This review aimed to present the current findings on the effect of prediagnosis physical activity on cancer incidence and mortality published between January 2019 and October 2024; this study summarizes the previous evidence, as well as the literature underlying biological mechanisms operating in the exercise–cancer relationship. The review also highlights gaps in the existing research and identifies future research directions. Methods: Medline/PubMed, ScienceDirect, and Google Scholar were searched with the search terms “physical activity” and “physical exercise” in conjunction with the MeSH terms for “cancer” and “carcinoma”. Primary, review, and meta-analysis studies published in English were included if they reported a measure of the effect size of prediagnosis physical activity on cancer incidence and/or cancer mortality. Results: Evidence from 37 observational studies and 10 reviews were included in this systematic review; 22 studies reported the effect of physical activity on cancer incidence, and 15 studies on cancer mortality. Of the 37 included observational studies, 19 confirmed the previous evidence that physical activity significantly decreased all-cancer-combined and cancer-specific site incidences, and 10 studies focused on cancer mortality. However, the molecular mechanisms involved in this process require future studies. The most convincing evidence maintains the effects of physical activity on body weight and fat, insulin resistance, sex hormones, regulation of redox homeostasis, enhancing the antioxidant defense system, and reducing oxidative stress. Conclusions: These data demonstrate substantial prevention against several cancer incidences and mortality among patients who performed regular physical activity, of which dose meets at least the WHO’s guidelines. Further prospective cohort studies and long-term RCT studies are warranted to address a safe and personalized activity dose for cancer-site prevention, identify more precisely the biological mechanisms operating in the physical activity–cancer relationship, and promote the benefits of being physically active.