Variants at chromosome 20 (ASIP locus) and melanoma risk
Cette étude européenne (837 cas et 1 154 témoins) évalue l'association entre 21 polymorphismes à simple nucléotide du locus ASIP sur le chromosome 20q11 et le risque de mélanome
ASIP locus on chromosome 20q11 is implicated, as shown by genome wide association studies (GWAS), in phenotype variation and melanoma risk. We genotyped 837 melanoma cases and 1154 controls for 21 single nucleotide polymorphisms (SNPs) informative for 495 polymorphisms at the locus. Our data showed an increased risk of melanoma (OR 1.27, 95%CI 1.03-1.57) in carriers of the rs4911414 variant, located 120 kb upstream of ASIP. The main effect of rs4911414, as reported previously, was in tandem with a 10 Kb adjacent polymorphism rs1015362; two constituted risk associated haplotype/diplotype. Except for rs1015363, none of the 12 tagging SNPs, genotyped to cover 239.9 kb region with polymorphisms linked to rs4911414 and rs1015362, were associated with melanoma. Our data confirmed a previous association of melanoma risk (OR 1.82, 95%CI 1.37-2.41) with rs4911442, located in intron 5 of the NCOA6 gene. The rs910871, one of the six variants, genotyped to cover NCOA6, showed an association with melanoma risk (OR 1.33, 95%CI 1.04-1.70). Both, rs4911442 and rs910871 were in moderate linkage with a, previously reported, risk associated rs910873 polymorphism. A haplotype from the variants within NCOA6 showed an association with risk of melanoma (OR 1.49, 95%CI 1.17-1.88). Interaction between risk associated polymorphisms and previously genotyped MC1R variants, in this study, was not statistically significant. Nevertheless, the carriers of the variants alleles over the background of MC1R variants were at a higher risk than the carriers not enriched for MC1R variants. Our data confirmed the association of different variants at chromosome 20q11 with melanoma risk.