Association of interferon regulatory factor-4 polymorphism rs12203592 with divergent melanoma pathways Journal Article
| Authors: | Gibbs, D. C.; Orlow, I.; Bramson, J. I.; Kanetsky, P. A.; Luo, L.; Kricker, A.; Armstrong, B. A.; Anton-Culver, H.; Gruber, S. B.; Marrett, L. D.; Gallagher, R. P.; Zanetti, R.; Rosso, S.; Dwyer, T.; Sharma, A.; La Pilla, E.; From, L.; Busam, K. J.; Cust, A. E.; Ollila, D. W.; Begg, C. B.; Berwick, M.; Thomas, N. E.; on behalf of the GEM Study Group |
| Article Title: | Association of interferon regulatory factor-4 polymorphism rs12203592 with divergent melanoma pathways |
| 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. ©The Author 2016. Published by Oxford University Press. All rights reserved. |
| Journal Title: | JNCI: Journal of the National Cancer Institute |
| Volume: | 108 |
| Issue: | 7 |
| ISSN: | 0027-8874 |
| Publisher: | Oxford University Press |
| Date Published: | 2016-07-01 |
| Start Page: | djw004 |
| Language: | English |
| DOI: | 10.1093/jnci/djw004 |
| PROVIDER: | scopus |
| PUBMED: | 26857527 |
| PMCID: | PMC4948568 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 August 2016 -- Source: Scopus |
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