Causal Association Between Skin Microbiota and Malignant Melanoma: Genetic Insights From Mendelian Randomization

Xianglong Li,1 Shuang Wu,2 Yujie Pan,3 Ziyan Wu,3 Zhong Du,1 Wanying Xie,1 Qingyu Zhou1 1Department of Medical and Radiation Oncology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 3School of Medicine, Yichun University, Yichun, People’s Republic of ChinaCorrespondence: Qingyu Zhou, Email [email protected]: Malignant melanoma (MM) is an extremely aggressive type of skin cancer that represents a major risk to human health. Earlier observational research has indicated that skin microbiota could play a role in the development and advancement of MM. Nevertheless, the causal link between skin microbiota and MM is still unclear.Methods: Utilizing data from genome-wide association studies (GWAS) conducted on a European cohort, we applied Mendelian randomization (MR) to evaluate the causal link between skin microbiota and MM. The analysis involved various MR methodologies, including inverse variance weighting (IVW), MR-Egger regression, weighted median, weighted mode and simple mode. Furthermore, we performed sensitivity analysis employing the intercept test of MR-Egger, the Cochran’s Q test, the MR-PRESSO approach, and a leave-one-out method.Results: By conducting MR analysis on the KORA FF4 cohort, we identified several skin microbiotas (ASV003 [Staphylococcus (unc).], ASV016 [Enhydrobacter (unc).], and ASV021 [Micrococcus (unc).]) related with an elevated risk of MM. Conversely, genus: Finegoldia and class: Alphaproteobacteria were shown to inhibit the occurrence of MM. Additionally, MR analysis of the PopGen cohort revealed that ASV021 [Micrococcus (unc).] and family: Moraxellaceae were identified as possible risk factors for MM.Conclusion: Our research offers new insights into the connection between skin microbiota and MM, indicating that skin microbiota might affect the onset and advancement of MM. Therefore, focusing on skin microbiota could be a valuable strategy for the prevention, identification, and management of MM.Keywords: Skin microbiota, Malignant melanoma, Genome-wide association study, Mendelian randomization