Physical activity in endometrial cancer prevention and control: Bridging epidemiological evidence to molecular mechanisms

Background: Since 2007, evidence supporting the role of physical activity (PA) in cancer prevention and survivorship has grown substantially. While early research focused on cancers such as colon, breast, and endometrial, more recent findings have consistently identified PA as a low-cost, broadly beneficial intervention across the cancer continuum. Among these, endometrial cancer has emerged as a site particularly responsive to physical activity, with robust epidemiological data indicating a significant preventive effect.

Methods: This presentation synthesizes findings from large-scale epidemiologic studies, pooled analyses, and recent prospective cohorts. A focused review was conducted of meta-analyses (e.g., pooled analysis of 33 studies with over 19,000 cases), along with clinical intervention trials assessing the impact of structured exercise programs in endometrial cancer survivors. Mechanistic insights were drawn from molecular and physiological studies exploring the metabolic, hormonal, and inflammatory pathways influenced by physical activity.

Results: Epidemiologic data demonstrate that women engaging in higher levels of physical activity experience approximately 18% reduced risk of developing endometrial cancer (RR = 0.81, 95% CI: 0.76–0.85). A dose-response relationship is evident, with each additional 1 MET-hour/week of activity corresponding to a ~0.2% risk reduction, translating to a 17% lower risk in total with 100 MET-hours/week. Mechanistic studies highlight several pathways through which PA exerts its protective effect, improved insulin sensitivity and weight regulation reduce circulating insulin and IGF-1 levels, increases in sex hormone-binding globulin lower bioavailable estrogen and chronic inflammation is mitigated via reductions in IL-6, TNF-α, and CRP, alongside activation of AMPK and inhibition of the PI3K/Akt/mTOR pathway. Intervention trials in survivors show high adherence (up to 80%) and clinically meaningful improvements in cardiorespiratory fitness, quality of life, body composition, and metabolic biomarkers.

Conclusions: Regular physical activity significantly reduces endometrial cancer risk and offers substantial benefits for survivors, influencing multiple biological pathways relevant to carcinogenesis and recovery. The integration of physical activity into clinical care and public health strategies represents a promising approach to reducing cancer burden and enhancing survivorship. Given its feasibility, safety, and wide-ranging benefits, physical activity should be prioritized as a core component of cancer prevention and control, especially for endometrial cancer.

Dr. Bai Peng has long been dedicated to research on physical activity and cancer prevention. He earned his Ph.D. at the West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University. Dr. Bai previously participated in global health programs at the CDC and has published extensively on studies linking cancer and lifestyle factors. He currently serves as the director of the Cancer Prevention and Rehabilitation Program at Sichuan University.