Unveiling the hidden causal links: skin flora and cutaneous melanoma.

Objective: The presence of skin flora (SF) has been identified as a significant factor in the onset and progression of cutaneous melanoma (CM). However, the vast diversity and abundance of SF present challenges to fully understanding the causal relationship between SF and CM. Methods: A Two Sample Mendelian Randomization (TSMR) analysis was conducted to investigating the causal relationship between SF and CM. The Inverse-Variance Weighted (IVW) method was utilized as the primary approach to assess the causal relationship under investigation. Furthermore, an independent external cohort was employed to validate the initial findings, followed by a meta-analysis of the consolidated results. To address potential confounding factors related to the influence of SF on CM, a Multivariate Mendelian Randomization (MVMR) analysis was also conducted. Finally, a Reverse Mendelian Randomization (RMR) was conducted to further validate the causal association. Results: TSMR results showed that 9 SF have a causal relationship with CM in the training cohort. Although these 9 SF weren't confirmed in the testing cohort, 4 SF remained significant in the meta-analysis after integrating results from both cohorts. MVMR analysis indicated that 3 SF were still significantly associated with CM after accounting for the interactions between different SF in the training cohort. No reverse causal relationship was identified in RMR analysis. Conclusion: A total of 9 SF were identified as having a potential causal relationship with CM; however, a large randomized controlled trial is needed to verify these results.