Genetic causality linking skin microbiota to skin cancer: Mendelian randomization study and meta-analysis

The skin microbiome has been linked to the etiology and progression of skin cancer, but the causal relationship remains unclear. This study employs two-sample Mendelian randomization (TSMR) and meta-analysis techniques to elucidate the putative genetic causal relationships between skin microbiota and skin cancer. Genetic variant data for the skin microbiome and skin cancer, drawn from large-scale genome-wide association studies, were extracted from European populations. TSMR analysis, heterogeneity tests, horizontal pleiotropy assessments, sensitivity analysis, and directional tests were conducted, followed by a meta-analysis to enhance the reliability of the findings. The TSMR and meta-analysis results indicate a significant association between the Proteobacteria phylum, including Gammaproteobacteria, and an increased risk of melanoma. Conversely, the Staphylococcus genus is significantly associated with a reduced risk of melanoma. Additionally, the Bacteroidetes phylum exhibits a statistically significant association with an elevated risk of basal cell carcinoma. This study furnishes genetic evidence substantiating the causal nexus between the skin microbiome and skin cancer. Further research is warranted to elucidate the underlying mechanisms and explore skin microbiome-centric prophylactic and therapeutic strategies for skin cancer.