An emulated target trial assessing the impact of physical activity on 14-year cancer risk: Insights from the Cancer Prevention Study-II.

Abstract

10541 Background: The American Cancer Society, along with the World Cancer Research Fund/American Institute of Cancer Research, recommends a weekly regimen of physical activity (at least 75 minutes of vigorous or 150 minutes of moderate-intensity aerobic physical activity) for cancer prevention. The positive impact of physical activity on reducing cancer risk is well-known; however, the causal link between physical activity and cancer risk reduction is not established, primarily due to the observational nature of the current evidence. Given the ethical considerations involved in assigning physical activity levels below the recommended minimum, coupled with the impracticality of conducting decades-long trials due to the latency period of cancer development, there is a need for an innovative approach beyond traditional observational and randomized trial methodologies. This highlights the importance of applying alternative strategies like emulated target trials to produce evidence of the causal effect of physical activity on cancer risk that would otherwise be difficult to obtain. This study aims to estimate the causal effect of adherence to recommended physical activity levels on the 14-year total cancer and obesity-related cancer risk using an emulated target trial framework. Methods: Data from 79,668 participants who were non-current smokers and without prevalent cancer diagnosis at pre-baseline in the Cancer Prevention Study-II were analyzed. This study estimated the effect of different physical activity levels (<7.5, 7.5-<15, and ≥15 MET-hrs/wk) on 14-year cancer risks using a parametric g-formula. Models adjusted for confounders include age, sex, education, years since quitting smoking, family history of cancer, physical activity, body mass index, alcohol consumption, diet quality (measured by the ACS diet score), history of cardiovascular disease, and diabetes. Results: Under no intervention, the estimated 14-year risk for any cancer was 27.9% (95% CI: 27.6%, 28.4%), and for obesity-related cancers, it was 11.2% (95% CI: 11.0%, 11.5%). Compared with no intervention, engaging in 7.5-<15 MET-hrs/wk of physical activity (minimum recommended) was linked with a 0.31% reduction in the risk of any cancer (95% CI: -0.41%, -0.06%) and a 0.19% reduction in the risk of obesity-related cancers (95% CI: -0.37%, -0.04%). Engaging in ≥15 MET-hrs/wk of physical activity (twice the minimum recommended level) was linked with a 1.31% risk reduction for any cancer (95% CI: -1.67%, -1.20%) and a 0.91% risk reduction for obesity-related cancers (95% CI: -1.09%, -0.80%), compared with no intervention. Conclusions: Incremental adherence to physical activity recommendations for cancer prevention could significantly lower the risk of developing cancers, including those related to obesity.