title: IRF4 variants have age-specific effects on nevus count and predispose to melanoma.
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 x 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 x 10(-3)), most significantly on the trunk (OR = 1.33, p = 2.5 x 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).
authors.affiliation: Queensland Institute of Medical Research, Brisbane 4029, Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Duffy
authors.forename: Mark M
authors.initials: MM
authors.lastname: Iles
authors.forename: Dan
authors.initials: D
authors.lastname: Glass
authors.forename: Gu
authors.initials: G
authors.lastname: Zhu
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Barrett
authors.forename: Veronica
authors.initials: V
authors.lastname: Höiom
authors.forename: Zhen Z
authors.initials: ZZ
authors.lastname: Zhao
authors.forename: Richard A
authors.initials: RA
authors.lastname: Sturm
authors.forename: Nicole
authors.initials: N
authors.lastname: Soranzo
authors.forename: Chris
authors.initials: C
authors.lastname: Hammond
authors.forename: Marina
authors.initials: M
authors.lastname: Kvaskoff
authors.forename: David C
authors.initials: DC
authors.lastname: Whiteman
authors.forename: Massimo
authors.initials: M
authors.lastname: Mangino
authors.forename: Johan
authors.initials: J
authors.lastname: Hansson
authors.forename: Julia A
authors.initials: JA
authors.lastname: Newton-Bishop
authors.forename: Veronique
authors.initials: V
authors.lastname: Bataille
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: D Timothy
authors.initials: DT
authors.lastname: Bishop
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D009506:Nevus / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012878:Skin Neoplasms / Q000235:genetics*; D055815:Young Adult; D000099218:Interferon Regulatory Factor-4
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D050835:Interferon Regulatory Factors; D000099218:Interferon Regulatory Factor-4