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

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.