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IRF4 Variants Have Age-Specific Effects on Nevus Count and Predispose to Melanoma
- Source :
-
American Journal of Human Genetics . Jul2010, Vol. 87 Issue 1, p6-16. 11p. - Publication Year :
- 2010
-
Abstract
- High melanocytic nevus count is a strong predictor of melanoma risk. A GWAS of nevus count in Australian adolescent twins identified an association of nevus count with the interferon regulatory factor 4 gene (IRF4 [p = 6 × 10−9]). There was a strong genotype-by-age interaction, which was replicated in independent UK samples of adolescents and adults. The rs12203592∗T allele was associated with high nevus counts and high freckling scores in adolescents, but with low nevus counts and high freckling scores in adults. The rs12203592∗T increased counts of flat (compound and junctional) nevi in Australian adolescent twins, but decreased counts of raised (intradermal) nevi. In combined analysis of melanoma case-control data from Australia, the UK, and Sweden, the rs12203592∗C allele was associated with melanoma (odds ratio [OR] 1.15, p = 4 × 10−3), most significantly on the trunk (OR = 1.33, p = 2.5 × 10−5). The melanoma association was corroborated in a GWAS performed by the GenoMEL consortium for an adjacent SNP, rs872071 (rs872071∗T: OR 1.14, p = 0.0035; excluding Australian, the UK, and Swedish samples typed at rs12203592: OR 1.08, p = 0.08). [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00029297
- Volume :
- 87
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- American Journal of Human Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 74125027
- Full Text :
- https://doi.org/10.1016/j.ajhg.2010.05.017