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PMID: 20602913 Published · ppublish English Journal Article Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Twin Study

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

American journal of human genetics ·Vol. 87 ·No. 1 ·2010-07-09 ·Pages 6-16

Duffy DL, Iles MM, Glass D, Zhu G, Barrett JH, Höiom V, Zhao ZZ, Sturm RA, Soranzo N, Hammond C, Kvaskoff M, Whiteman DC, Mangino M, Hansson J, Newton-Bishop JA, GenoMEL, Bataille V, Hayward NK, Martin NG, Bishop DT, Spector TD, Montgomery GW

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).

MeSH Terms
Adolescent Adult Age Factors Aged Aged, 80 and over Case-Control Studies Child Cyclin-Dependent Kinase Inhibitor p16/genetics Female Genetic Predisposition to Disease Genome-Wide Association Study Humans Interferon Regulatory Factors/genetics Male Melanoma/genetics Middle Aged Nevus/genetics Polymorphism, Single Nucleotide Skin Neoplasms/genetics Young Adult
Chemicals
Cyclin-Dependent Kinase Inhibitor p16 Interferon Regulatory Factors interferon regulatory factor-4
Authors & Affiliations
22 authors, click to expand affiliations / ORCID
Duffy David L
Queensland Institute of Medical Research, Brisbane 4029, Australia.
Iles Mark M
Glass Dan
Zhu Gu
Barrett Jennifer H
Höiom Veronica
Zhao Zhen Z
Sturm Richard A
Soranzo Nicole
Hammond Chris
Kvaskoff Marina
Whiteman David C
Mangino Massimo
Hansson Johan
Newton-Bishop Julia A
GenoMEL
Bataille Veronique
Hayward Nicholas K
Martin Nicholas G
Bishop D Timothy
Spector Timothy D
Montgomery Grant W
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
1537-6605
DOI
10.1016/j.ajhg.2010.05.017
Published
2010-07-09
Epub
2010-00-17
Pages
6-16
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC2896771
Subset
IM
Grants
NCI NIH HHS · R01 CA083115 · United States
Cancer Research UK · C8216/A6129 · United Kingdom
NCI NIH HHS · R01 CA83115. · United States
NCI NIH HHS · CA88363 · United States
NCI NIH HHS · R01 CA83115 · United States
Cancer Research UK · C588/A10721 · United Kingdom
NCI NIH HHS · R01 CA088363 · United States
Cancer Research UK · 10589 · United Kingdom
Medical Research Council · G0900339 · United Kingdom
Cancer Research UK · C588/A499 · United Kingdom
External Links
PubMed source DOI: 10.1016/j.ajhg.2010.05.017 PMC Full Text View journal details
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