Genetic Causal Relationship Between Sex Hormones and Basal Cell Carcinoma: A Two-Sample Mendelian Randomization Study

Background: The primary aim of this study was to explore whether sex hormones affect the occurrence of basal cell carcinoma (BCC) from a genetic perspective using a two-sample Mendelian randomization (MR) study. Methods: Exposure and outcome data for this MR analysis were derived from previously published GWAS studies. In this study, estradiol, sex hormone-binding globulin (SHBG), bioavailable testosterone, and total testosterone were used as exposures, and BCC was used as the outcome for the two-sample MR analysis. The random effects inverse variance weighted (IVW) model was the primary analytical model, and the simple mode, weighted median, MR-Egger, and weighted mode methods were applied as complementary approaches. Furthermore, the "leave-one-out" sensitivity analysis was performed to assess stability, Cochran's Q test to evaluate heterogeneity, and the MR-Egger intercept test to analyze horizontal multiplicity. Results: The two-sample MR analysis of the sex hormone and BCC showed that estradiol, sex hormone-binding globulin (SHBG), bioavailable testosterone, and total testosterone were not a causal factor in BCC (P>0.05). The results of the heterogeneity test and horizontal pleiotropic analysis showed that no heterogeneity or horizontal pleiotropic existed in all MR analyses (Cochran's Q-P>0.05, Conclusion: The two-sample MR analysis showed that estrogen and testosterone did not affect the occurrence and development of BCC at the genetic level.