Causal relationship between sex hormones and cutaneous melanoma: a two-sample Mendelian randomized study

This study aimed to elucidate the genetic aspects of the relationship between sex hormones and cutaneous melanoma risk, providing valuable insights into this complex association. In this study, we used estradiol, bioavailable testosterone, sex hormone-binding globulin, and total testosterone as the exposure and melanoma as the outcome for two-sample Mendelian randomization analysis. In this study, a random-effects inverse-variance weighting (IVW) model was used as the main analysis model, and the corresponding weighted median, simple mode, weighted mode, and Mendelian randomization‒Egger methods were used as supplementary methods. We assessed both heterogeneity and horizontal pleiotropy in our study, scrutinizing whether the analysis results were affected by any individual single nucleotide polymorphism. The random-effects IVW method indicated that estradiol [odds ratio (OR), 1.000; 95% confidence interval (CI), 0.998-1.003; P  = 0.658], bioavailable testosterone (OR = 1.001, 95% CI, 0.999-1.003; P  = 0.294), sex hormone-binding globulin (IVW: OR, 1.000; 95% CI, 0.998-1.003; P  = 0.658), and total testosterone (IVW: OR, 1.002; 95% CI, 0.999-1.005; P  = 0.135) were not genetically linked to cutaneous melanoma. No analyses exhibited heterogeneity, horizontal pleiotropy, or deviations. We were unable to find genetic evidence for a causal relationship between sex hormones and the occurrence of cutaneous melanoma in this study. These results are limited by sample size and population, so the causal relationship between sex hormones and cutaneous melanoma needs to be further studied.