Association of interferon regulatory factor-4 polymorphism rs12203592 with divergent melanoma pathways

David C. Gibbs, Irene Orlow, Jennifer I. Bramson, Peter A. Kanetsky, Li Luo, Anne Kricker, Bruce A. Armstrong, Hoda Anton-Culver, Stephen B. Gruber, Loraine D. Marrett, Richard P. Gallagher, Roberto Zanetti, Stefano Rosso, Terence Dwyer, Ajay Sharma, Emily La Pilla, Lynn From, Klaus J. Busam, Anne E. Cust, David W. OllilaColin B. Begg, Marianne Berwick, Nancy E. Thomas

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23 Citations (Scopus)

Abstract

Background: Solar elastosis and neval remnants are histologic markers characteristic of divergent melanoma pathways linked to differences in age at onset, host phenotype, and sun exposure. However, the association between these pathway markers and newly identified low-penetrance melanoma susceptibility loci remains unknown. Methods: In the Genes, Environment and Melanoma (GEM) Study, 2103 Caucasian participants had first primary melanomas that underwent centralized pathology review. For 47 single-nucleotide polymorphisms (SNPs) previously identified as lowpenetrant melanoma risk variants, we used multinomial logistic regression to compare melanoma with solar elastosis and melanoma with neval remnants simultaneously to melanoma with neither of these markers, excluding melanomas with both markers. All statistical tests were two-sided. Results: IRF4 rs12203592 was the only SNP to pass the false discovery threshold in baseline models adjusted for age, sex, and study center. rs12203592 T was associated positively with melanoma with solar elastosis (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.18 to 1.82) and inversely with melanoma with neval remnants (OR = 0.65, 95% CI = 0.48 to 0.87) compared with melanoma with neither marker (Pglobal = 3.78 x 10-08). Adjusting for phenotypic characteristics and total sun exposure hours did not materially affect rs12203592's associations. Distinct early- and late-onset age distributions were observed in patients with IRF4 rs12203592 [CC] and [TT] genotypes, respectively.

Original languageEnglish
JournalJournal of the National Cancer Institute
Volume108
Issue number7
DOIs
Publication statusPublished - Jul 2016
Externally publishedYes

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