IRF4 variants have age-specific effects on nevus count and predispose to melanoma

Duffy, D.L. et al. (2010) IRF4 variants have age-specific effects on nevus count and predispose to melanoma. American Journal of Human Genetics, 87(1), pp. 6-16. (doi: 10.1016/j.ajhg.2010.05.017)

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).

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: UNSPECIFIED
• Authors: Duffy, D.L., Iles, M.M., Glass, D., Zhu, G., Barrett, J.H., Höiom, V., Zhao, Z.Z., Sturm, R.A., Soranzo, N., Hammond, C., Kvaskoff, M., Whiteman, D.C., Mangino, M., Hansson, J., Newton-Bishop, J.A., GenoMEL, , Bataille, V., Hayward, N.K., Martin, N.G., Bishop, D.T., Spector, T.D., and Montgomery, G.W.
• College/School: College of Medical Veterinary and Life Sciences
• Research Group: Melanoma Genetics Consortium
• Journal Name: American Journal of Human Genetics
• ISSN: 0002-9297
• Published Online: 09 July 2010