Mendelian randomization analysis of the causal association between metabolites and skin cancer

Skin cancer (SC) is a significant public health issue, with increasing incidence rates globally. Although environmental factors such as ultraviolet radiation (UVR) exposure are recognized risk factors, the impact of metabolites on SC development has not been thoroughly examined. This study seeks to explore the causal association between metabolites and SC risks using a Mendelian randomization (MR) approach. Our analysis identified 76 metabolites associated with SC risk. Of them, the leucine-to-N-palmitoylsphingosine ratio, glycerol-to-palmitoylcarnitine ratio, oleoyllinoleoyl-glycerol levels, and hypotaurine-to-taurine ratio were strongly associated with SC. Notably, the leucine-to-N-palmitoylsphingosine ratio and the glycerol-to-palmitoylcarnitine ratio were associated with increased risk factors for SC. However, oleoyllinoleoyl-glycerol levels and hypotaurine-to-taurine ratio served as the protective indicators of SC. This study highlights the potential role of metabolites in skin cancer etiology, suggesting that metabolic factors may serve as important targets for prevention and risk assessment strategies.