Causal relationship among immune cells, basal cell carcinoma, and gut microbiome: a two-sample Mendelian randomization analysis and mediation analysis

Research studies suggest that the host immune system is modulated by gut microbiota (GM), which is crucial for the occurrence and progression of malignancies. Here, immune cell traits (ICTs) as mediating factors in the causative association between basal cell cancer (BCC) and gut microbiome were investigated. A two-sample Mendelian randomization (MR) analysis was undertaken to assess the influence of 412 GMs on BCC using data from a genome-wide association study (GWAS) of individuals with European ancestry. Afterward, the ICTs' mediation effect on the relationships between BCC and GM was examined using MR. Inverse variance weighted method identified 9 genera and 47 ICTs that were genetically associated with BCC. Moreover, the MR demonstrated that CD33-HLA DR-AC (- 0.015, 95% CI - 0.144, 0.115) mediated a portion of the causative function of p_Firmicutes.c_Clostridia on BCC, it represented - 8.92% of the total effect. The current research elucidated the causal association between BCC risk, GM, and certain ICTs. This also explained the mechanism and offered potential BCC therapeutic options and preventive targets against the disease.