Association of inherited genetic variants with multiple primary melanoma.

Background: Recent genome-wide association studies (GWAS) have identified new susceptibility loci for melanoma, but their associations with multiple primary melanoma (MPM) are unclear.

Methods: We investigated the associations of 69 single nucleotide polymorphisms (SNPs) in 39 GWAS-identified loci with odds of MPM relative to single primary melanoma (SPM) in the international, population-based Genes, Environment, and Melanoma (GEM) study. Per-minor allele odds ratios (ORs) and 95% confidence intervals (CIs) for individuals with MPM 'cases' (n=1,205) relative to SPM 'controls' (n=2,458) were estimated using multivariable logistic regression, and polygenic risk scores (PRS) were calculated and weighted based on a 2020 GWAS meta-analysis (57 of the 68 independent GWAS SNPs available).