Melanoma Expression Genes Identified through Genome-Wide Association Study of Breslow Tumor Thickness

Abstract

rs12203592 falls within an enhancer region of IRF4; the T allele impairs transcription factor binding, leading to reduced expression of IRF4 and tyrosinase (Praetorius et al., 2013). In a recent meta-analysis, the association between rs12203592 polymorphism and SCC was significant in dominant, recessive, and codominant models (Wu et al., 2016). The additive genetic model was selected a priori for our study, but exploration of the codominant model confirmed the association between SCC risk and the TT versusCCgenotype (HR1⁄4 2.24, 95% confidence interval 1⁄4 1.22e4.09, P 1⁄4 0.009). Previous studies investigating genetic risks for cSCC in OTRs have been limited by small sample sizes and candidate gene approach; the recent GWAS for cSCC has informed our candidate gene selection in this cohort. Our study design enabled investigation of these genes in the context of Fitzpatrick skin type, an important risk factor. Our data show that genotype data can improve risk stratification for posttransplantation cSCC beyond the clinical pigmentation phenotype. Strengths of this study include a wellcharacterized cohort with Fitzpatrick type and histopathologic confirmation of cSCC outcomes. The genotyping array is the same as that used in Asgari et al. (2016), allowing direct validation of SNPs reported in that publication. The primary limitation is small sample size, but this pilot data supports development of cohort studies to generate