Genome-wide association study identifies variants at 9p21 and 22q13 associated with development of cutaneous nevi

Top Cited Papers
Publisher Website
Google Scholar
Abstract
Timothy Spector, Mario Falchi and colleagues report a genome-wide association study for development of cutaneous nevi, the strongest known risk factor for cutaneous melanoma. They report two loci associated with nevus count, and show these loci are also associated with susceptibility to melanoma. A high melanocytic nevi count is the strongest known risk factor for cutaneous melanoma. We conducted a genome-wide association study for nevus count using 297,108 SNPs in 1,524 twins, with validation in an independent cohort of 4,107 individuals. We identified strongly associated variants in MTAP, a gene adjacent to the familial melanoma susceptibility locus CDKN2A on 9p21 (rs4636294, combined P = 3.4 × 10−15), as well as in PLA2G6 on 22q13.1 (rs2284063, combined P = 3.4 × 10−8). In addition, variants in these two loci showed association with melanoma risk in 3,131 melanoma cases from two independent studies, including rs10757257 at 9p21, combined P = 3.4 × 10−8, OR = 1.23 (95% CI = 1.15–1.30) and rs132985 at 22q13.1, combined P = 2.6 × 10−7, OR = 1.23 (95% CI = 1.15–1.30). This provides the first report of common variants associated to nevus number and demonstrates association of these variants with melanoma susceptibility.