TY - JOUR
AU - Group GEM
AU - Thomas Nancy
AU - Edmiston Sharon
AU - Kanetsky Peter
AU - Busam Klaus
AU - Kricker Anne
AU - Armstrong Bruce
AU - Cust Anne
AU - Anton-Culver Hoda
AU - Gruber Stephen
AU - Luo Li
AU - Orlow Irene
AU - Gallagher Richard
AU - Zanetti Roberto
AU - Rosso Stefano
AU - Sacchetto Lidia
AU - Parrish Eloise
AU - Hao Honglin
AU - Gibbs David
AU - Ollila David
AU - Begg Colin
AU - Berwick Marianne
AU - Conway Kathleen
AU - Dwyer Terence
AB - <p>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 (GEM) Study, 1223 European-origin participants had their incident invasive primary melanomas screened for BRAF/NRAS mutations and germline DNA genotyped for 47 single-nucleotide polymorphisms (SNPs) identified as low-penetrant melanoma risk variants. We used multinomial logistic regression to simultaneously examine each SNP'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 (OR = 0.59, 95% 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 (P = 0.001) passed false discovery (P = 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 (P) 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.</p>
BT - J Invest Dermatol
C1 - https://www.ncbi.nlm.nih.gov/pubmed/29753029?dopt=Abstract
DO - 10.1016/j.jid.2018.04.025
J2 - J. Invest. Dermatol.
LA - eng
N2 - <p>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 (GEM) Study, 1223 European-origin participants had their incident invasive primary melanomas screened for BRAF/NRAS mutations and germline DNA genotyped for 47 single-nucleotide polymorphisms (SNPs) identified as low-penetrant melanoma risk variants. We used multinomial logistic regression to simultaneously examine each SNP'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 (OR = 0.59, 95% 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 (P = 0.001) passed false discovery (P = 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 (P) 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.</p>
PY - 2018
T2 - J Invest Dermatol
TI - Inherited Genetic Variants Associated with Melanoma BRAF/NRAS Subtypes.
SN - 1523-1747
ER -