Abstract
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 x 10(-15)), as well as in PLA2G6 on 22q13.1 (rs2284063, combined P = 3.4 x 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 x 10(-8), OR = 1.23 (95% CI = 1.15-1.30) and rs132985 at 22q13.1, combined P = 2.6 x 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.
Original language | English |
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Pages (from-to) | 915 - 919 |
Number of pages | 5 |
Journal | Nature Genetics |
Volume | 41 |
Issue number | 8 |
DOIs | |
Publication status | Published - Aug 2009 |
Keywords
- Alleles
- Chromosomes, Human, Pair 22
- Chromosomes, Human, Pair 9
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Great Britain
- Homozygote
- Humans
- Melanoma
- Nevus
- Polymorphism, Single Nucleotide
- Precancerous Conditions
- Skin Neoplasms