Polymorphisms of the MATP/SLC45A2 gene and susceptibility to melanoma in the French population

Abstract

11040 Background: Loss-of-function variants in the melanocortin 1 receptor gene (MC1R) are low penetrant melanoma predisposing alleles. Methods: A cohort comprising 1,019 patients affected by melanoma (MelanCohort) and 1,466 Caucasian controls skin cancer-free were studied. Ten polymorphisms, including five functional MC1R alleles (R151C, R160W, D294H, R142H, D84E), two non-synonymous SLC45A2 variants (L374F and E272K), and three intronic OCA2 variants previously shown to be strongly associated with eye color (rs7495174, rs4778241 and rs4778138) were genotyped. Genotype, allele, haplotype and diplotype frequencies were compared in the two groups using Fisher’s exact test and odds ratio calculations Results: As expected, MC1R variants were closely associated with melanoma risk (P-value < 2.20×10-16). Interestingly, the SLC45A2 variants L374F and E272K were also significantly and strongly associated with melanoma (respectively, P-value × 2.12×10-15, OR × 0.35 [0.26–0.46], and P-value = 1.10×10-6 OR × 0.40 [0.27–0.59]). MC1R and SLC45A2 variants had additive effects on melanoma risk, and after adjusting for clinical risk factors, the risk was persistent, even though both genes were strongly associated with pigmentation. Conclusions: Future studies may show whether genetic information could provide a useful complement to physical examination in predicting melanoma risk. No significant financial relationships to disclose.