Potential Risk of Cutaneous Melanoma Attributable to Medication Use: A Mendelian Randomization Approach

Background/Objective: Cutaneous melanoma is a highly heterogeneous malignancy and life-threatening skin cancer with rising global incidence. Although various therapeutic options are available, their clinical efficacy remains limited, highlighting the urgent need for novel strategies that facilitate prevention, diagnosis, and treatment. The aim of this study was to explore the potential causal association between medication use and the risk of developing cutaneous melanomas. Methods: Using summary data from Genome-Wide Association Studies (GWASs), we performed Mendelian randomization (MR) to investigate the causal effect of medication use on cutaneous melanoma risk. Exposure data were based on self-reported medication uses from ~320,000 European participants in the UK Biobank. The outcomes included GWAS results from 2824 cutaneous melanoma cases. Single-nucleotide polymorphisms (SNPs) significantly associated with medication use were used as instruments and analyzed with IVW, weighted median, weighted mode, and MR-Egger methods. Sensitivity analyses were used to assess pleiotropy and heterogeneity. Results: The analysis revealed that genetically predicted high use of adrenergics, inhalers, glucocorticoids, and opioids was suggestively associated with a reduced risk of cutaneous melanoma. Sensitivity analyses supported the robustness of these findings, showing no evidence of horizontal pleiotropy or influence from outliers. Conclusions: The results presented herein suggest that certain medication uses may lower the risk of developing cutaneous melanomas, offering potential new avenues for future prevention and treatment strategies.