The causal effects of childhood sunburn occasions on melanoma: A univariable and multivariable Mendelian randomization study.

Observational studies have shown an association between childhood sunburn occasions (CSOs) and melanoma in situ (MIS). However, these studies have shown contradictory results. Here, we used a two-sample Mendelian randomization (MR) method to make a causal inference between CSOs and melanoma at the genetic level. Based on the publicly available genome-wide association study summary data, including childhood sunburn (n = 346,955) and MIS (n = 218,792), the inverse-variance weighted (IVW) method of the random effects model was used, supplemented by the MR-Egger method, the weighted median method, and the weighted mode method. IVW results showed a 2.58-fold increased risk of melanoma development for each standard deviation increase in CSOs (odds ratio [OR] = 3.58; 95% confidence interval [CI]: 1.68-7.64; P = 1.00 × 10-3), with the MR-Egger (OR = 4.76, 95% CI: 1.65-13.75, P = 5.60 × 10-3), weighted median (OR = 4.89, 95% CI: 1.62-14.76, P = 4.90 × 10-3), and weighted mode (OR = 6.26, 95% CI: 2.49-15.77, P = 3.00 × 10-4) supporting the results. Furthermore, both the funnel plot and the MR-Egger intercepts showed the absence of directional pleiotropy between childhood sunburn and MIS. Our study confirmed that CSOs increase the risk of melanoma development.