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

Duffy, David L., Iles, Mark M., Glass, Dan, Zhu, Gu, Barrett, Jennifer H., Hoiom, Veronica, Zhao, Zhen Z., Sturm, Richard A., Soranzo, Nicole, Hammond, Chris, Kvaskoff, Marina, Whiteman, David C., Mangino, Massimo, Hansson, Johan, Newton-Bishop, Julia A., Bataille, Veronique, Hayward, Nicholas K., Martin, Nicholas G., Bishop, D. Timothy, Spector, Timothy D. and Montgomery, Grant W. (2010) IRF4 variants have age-specific effects on nevus count and predispose to melanoma. American Journal of Human Genetics, 87 1: 6-16. doi:10.1016/j.ajhg.2010.05.017

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Author Duffy, David L.
Iles, Mark M.
Glass, Dan
Zhu, Gu
Barrett, Jennifer H.
Hoiom, Veronica
Zhao, Zhen Z.
Sturm, Richard A.
Soranzo, Nicole
Hammond, Chris
Kvaskoff, Marina
Whiteman, David C.
Mangino, Massimo
Hansson, Johan
Newton-Bishop, Julia A.
Bataille, Veronique
Hayward, Nicholas K.
Martin, Nicholas G.
Bishop, D. Timothy
Spector, Timothy D.
Montgomery, Grant W.
Title IRF4 variants have age-specific effects on nevus count and predispose to melanoma
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
1537-6605
Publication date 2010-07
Sub-type Article (original research)
DOI 10.1016/j.ajhg.2010.05.017
Volume 87
Issue 1
Start page 6
End page 16
Total pages 11
Place of publication Cambridge, MA, U.S.A.
Publisher Cell Press
Collection year 2011
Language eng
Formatted 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 rs12203592T 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 rs12203592T 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 rs12203592C 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 (rs872071T: OR 1.14, p = 0.0035; excluding Australian, the UK, and Swedish samples typed at rs12203592: OR 1.08, p = 0.08).
© 2010 The American Society of Human Genetics. All rights reserved.

Keyword Genome-wide association
Cutaneous melanoma
Familial aggregation
Pooled analysis
Sun exposure
Risk-factors
Adult twins
Pigmentation
Density
Gene
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Sun, 08 Aug 2010, 00:09:43 EST