The Causal Relationship Between Physical Activity and Skin Cancer Risk: An Univariable Mendelian Randomization Study

Background: The existing observational research on the relationship between physical activity (PA) and skin cancer (SC) is contentious, which points to the intricate nature of their association and underscores the imperative for more nuanced research to untangle the causal dynamics at play. The aim of this article is to delve deeper into this complex relationship, seeking to clarify whether PA serves as a protective factor against SC, or contributes to its risk. Methods: We utilized data from the genome-wide association study (GWAS) of PA from GWAS Catalog (include self-reported moderate to vigorous PA (MVPA), self-reported vigorous PA (VPA), and accelerometer-based average-accelerated PA). The data of SC is from FinnGen. All of the participants are of European ancestry. We used two-sample Mendelian Randomization (TSMR) to analyze the causal relationship between PA and SC.The research was conducted using inverse variance weighted (IVW) method as the primary approach, and MR Egger regression as supplementary analytical method. To ensure the robustness of the results, Cochran's Q-test and MR pleiotropy residual sum and outlier (MR-PRESSO) global tests were used to measure sensitivity. Results: Our analysis indicated that average-accelerated PA was associated with an increased risk of SC (ORIVW IVW = 0.94, 95% CI 0.93-0.96, P < 0.001). While neither MVPA (ORIVW IVW = 0.99, 95% CI 0.67-1.47, P = 0.962) nor VPA (ORIVW IVW = 0.80, 95% CI 0.29-2.18, P = 0.656) shows causal relationship on risk of SC. Conclusion: Our research suggests that PA is associated with a decrease in SC, provides a new perspective for future SC prevention. Our research findings bolster the hypothesis that increased levels of PA, characterized by average acceleration, are associated with a reduced risk of developing skin cancer. This has filled the gap of research on the causal relationship between PA and SC, and could pave the way for novel preventive strategies against skin cancer.