Inherited genetic variants associated with melanoma BRAF/NRAS subtypes Journal Article


Authors: Thomas, N. E.; Edmiston, S. N.; Orlow, I.; Kanetsky, P. A.; Luo, L.; Gibbs, D. C.; Parrish, E. A.; Hao, H.; Busam, K. J.; Armstrong, B. K.; Kricker, A.; Cust, A. E.; Anton-Culver, H.; Gruber, S. B.; Gallagher, R. P.; Zanetti, R.; Rosso, S.; Sacchetto, L.; Dwyer, T.; Ollila, D. W.; Begg, C. B.; Berwick, M.; Conway, K.; on behalf of the G. E. M. Study Group
Contributors: Berwick, M.; Roy, P.; Reiner, A.; Leong, S.; Corrales Guerrero, S.; Sadeghi, K.
Article Title: Inherited genetic variants associated with melanoma BRAF/NRAS subtypes
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. © 2018 The Authors
Keywords: adult; controlled study; major clinical study; single nucleotide polymorphism; phenotype; melanoma; gene locus; genetic variability; genotype; dna; b raf kinase; interferon regulatory factor 4; oncogene n ras; human; male; female; priority journal; article
Journal Title: Journal of Investigative Dermatology
Volume: 138
Issue: 11
ISSN: 0022-202X
Publisher: Nature Publishing Group  
Date Published: 2018-11-01
Start Page: 2398
End Page: 2404
Language: English
DOI: 10.1016/j.jid.2018.04.025
PUBMED: 29753029
PROVIDER: scopus
PMCID: PMC6200630
DOI/URL:
Notes: Article -- Export Date: 1 November 2018 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Anne S Reiner
    120 Reiner
  2. Colin B Begg
    236 Begg
  3. Marianne Berwick
    119 Berwick
  4. Irene Orlow
    191 Orlow
  5. Klaus J Busam
    536 Busam
  6. Pampa Roy
    32 Roy
  7. Siok Fun Leong
    4 Leong