학술논문
Inherited Genetic Variants Associated with Melanoma BRAF/NRAS Subtypes
Document Type
article
Author
Thomas, Nancy E; Edmiston, Sharon N; Orlow, Irene; Kanetsky, Peter A; Luo, Li; Gibbs, David C; Parrish, Eloise A; Hao, Honglin; Busam, Klaus J; Armstrong, Bruce K; Kricker, Anne; Cust, Anne E; Anton-Culver, Hoda; Gruber, Stephen B; Gallagher, Richard P; Zanetti, Roberto; Rosso, Stefano; Sacchetto, Lidia; Dwyer, Terence; Ollila, David W; Begg, Colin B; Berwick, Marianne; Conway, Kathleen; Begg, Colin; Roy, Pampa; Reiner, Anne; Leong, Siok; Guerrero, Sergio Corrales; Sadeghi, Keimya; Boyce, Tawny W; Venn, Alison; Tucker, Paul; Marrett, Loraine D; From, Lynn; Huang, Shu-Chen; Groben, Pamela A; Parrish, Eloise; Frank, Jill S; Rebbeck, Timothy R; Taylor, Julia Lee; Madronich, Sasha
Source
Journal of Investigative Dermatology. 138(11)
Subject
Language
Abstract
BRAF and NRAS mutations arise early in melanoma development, but their associations with low-penetrance melanoma susceptibility loci remain unknown. In the Genes, Environment and Melanoma Study, 1,223 European-origin participants had their incident invasive primary melanomas screened for BRAF/NRAS mutations and germline DNA genotyped for 47 single-nucleotide polymorphisms identified as low-penetrant melanoma-risk variants. We used multinomial logistic regression to simultaneously examine each single-nucleotide polymorphism's relationship to BRAF V600E, BRAF V600K, BRAF other, and NRAS+ relative to BRAF-/NRAS- melanoma adjusted for study features. IRF4 rs12203592*T was associated with BRAF V600E (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.43-0.79) and V600K (OR = 0.65, 95% CI = 0.41-1.03), but not BRAF other or NRAS+ melanoma. A global test of etiologic heterogeneity (Pglobal = 0.001) passed false discovery (Pglobal = 0.0026). PLA2G6 rs132985*T was associated with BRAF V600E (OR = 1.32, 95% CI = 1.05-1.67) and BRAF other (OR = 1.82, 95% CI = 1.11-2.98), but not BRAF V600K or NRAS+ melanoma. The test for etiologic heterogeneity (Pglobal) was 0.005. The IRF4 rs12203592 associations were slightly attenuated after adjustment for melanoma-risk phenotypes. The PLA2G6 rs132985 associations were independent of phenotypes. IRF4 and PLA2G6 inherited genotypes may influence melanoma BRAF/NRAS subtype development.