Details

Autor(en) / Beteiligte

• 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.
• Lee Taylor, Julia
• Madronich, Sasha

Titel

Inherited Genetic Variants Associated with Melanoma BRAF/NRAS Subtypes

Ist Teil von

• Journal of investigative dermatology, 2018-11, Vol.138 (11), p.2398-2404

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.