@article{22376,
  author = {Kanetsky P. and Dwyer T and Gibbs D. and Orlow I. and Luo L. and Kricker A. and Armstrong B. and Anton-Culver H. and Gruber S. and Marrett L. and Gallagher R. and Zanetti R. and Rosso S. and Sharma A. and La Pilla E. and From L. and Busam K. and Cust A. and Ollila D. and Begg C. and Berwick M. and Thomas N. and Bramson J.},
  title = {Association of Interferon Regulatory Factor-4 Polymorphism rs12203592 With Divergent Melanoma Pathways},
  abstract = {<p>
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 low-penetrant 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 (P global = 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. CONCLUSIONS: Our findings suggest a role of IRF4 rs12203592 in pathway-specific risk for melanoma development. We hypothesize that IRF4 rs12203592 could underlie in part the bimodal age distribution reported for melanoma and linked to the divergent pathways.
</p>
},
  year = {2016},
  journal = {Journal of the National Cancer Institute},
  volume = {108},
  edition = {2016/02/10},
  number = {7},
  isbn = {1460-2105 (Electronic)<br/>0027-8874 (Linking)},
  note = {Gibbs, David C<br/>Orlow, Irene<br/>Bramson, Jennifer I<br/>Kanetsky, Peter A<br/>Luo, Li<br/>Kricker, Anne<br/>Armstrong, Bruce K<br/>Anton-Culver, Hoda<br/>Gruber, Stephen B<br/>Marrett, Loraine D<br/>Gallagher, Richard P<br/>Zanetti, Roberto<br/>Rosso, Stefano<br/>Dwyer, Terence<br/>Sharma, Ajay<br/>La Pilla, Emily<br/>From, Lynn<br/>Busam, Klaus J<br/>Cust, Anne E<br/>Ollila, David W<br/>Begg, Colin B<br/>Berwick, Marianne<br/>Thomas, Nancy E<br/>GEM Study Group<br/>P30 CA016086/CA/NCI NIH HHS/United States<br/>R01 CA112243/CA/NCI NIH HHS/United States<br/>R01 CA112524/CA/NCI NIH HHS/United States<br/>United States<br/>J Natl Cancer Inst. 2016 Feb 8;108(7). pii: djw004. doi: 10.1093/jnci/djw004. Print 2016 Jul.},
  language = {eng},
}