Associations of MC1R genotype and patient phenotypes with BRAF and NRAS mutations in melanoma Journal Article


Authors: Thomas, N. E.; Edmiston, S. N.; Kanetsky, P. A.; Busam, K. J.; Kricker, A.; Armstrong, B. K.; Cust, A. E.; Anton-Culver, H.; Gruber, S. B.; Luo, L.; Orlow, I.; Reiner, A. S.; Gallagher, R. P.; Zanetti, R.; Rosso, S.; Sacchetto, L.; Dwyer, T.; Parrish, E. A.; Hao, H.; Gibbs, D. C.; Frank, J. S.; Ollila, D. W.; Begg, C. B.; Berwick, M.; Conway, K.; on behalf of the GEM Study Group
Contributors: Roy, P.; Patel, H.
Article Title: Associations of MC1R genotype and patient phenotypes with BRAF and NRAS mutations in melanoma
Abstract: Associations of MC1R with BRAF mutations in melanoma have been inconsistent between studies. We sought to determine for 1,227 participants in the international population-based Genes, Environment, and Melanoma (GEM) study whether MC1R and phenotypes were associated with melanoma BRAF/NRAS subtypes. We used logistic regression adjusted by age, sex, and study design features and examined effect modifications. BRAF+ were associated with younger age, blond/light brown hair, increased nevi, and less freckling, and NRAS+ with older age relative to the wild type (BRAF–/NRAS–) melanomas (all P < 0.05). Comparing specific BRAF subtypes to the wild type, BRAF V600E was associated with younger age, blond/light brown hair, and increased nevi and V600K with increased nevi and less freckling (all P < 0.05). MC1R was positively associated with BRAF V600E cases but only among individuals with darker phototypes or darker hair (Pinteraction < 0.05) but inversely associated with BRAF V600K (Ptrend = 0.006) with no significant effect modification by phenotypes. These results support distinct etiologies for BRAF V600E, BRAF V600K, NRAS+, and wild-type melanomas. MC1R's associations with BRAF V600E cases limited to individuals with darker phenotypes indicate that MC1R genotypes specifically provide information about BRAF V600E melanoma risk in those not considered high risk based on phenotype. Our results also suggest that melanin pathways deserve further study in BRAF V600E melanomagenesis. © 2017 The Authors
Keywords: adult; aged; middle aged; gene mutation; major clinical study; genetics; mutation; united states; phenotype; melanoma; nevus; skin neoplasms; membrane proteins; genetic association; genotype; wild type; age; hair color; skin tumor; membrane protein; australia; gender; logistic regression analysis; melanocortin 1 receptor; receptor, melanocortin, type 1; b raf kinase; proto-oncogene proteins b-raf; braf protein, human; gtp phosphohydrolases; guanosine triphosphatase; oncogene n ras; mc1r gene; lentigo; humans; human; male; female; priority journal; article; nras protein, human
Journal Title: Journal of Investigative Dermatology
Volume: 137
Issue: 12
ISSN: 0022-202X
Publisher: Nature Publishing Group  
Date Published: 2017-12-01
Start Page: 2588
End Page: 2598
Language: English
DOI: 10.1016/j.jid.2017.07.832
PUBMED: 28842324
PROVIDER: scopus
PMCID: PMC5701875
DOI/URL:
Notes: Article -- Export Date: 2 January 2018 -- Source: Scopus
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MSK Authors
  1. Anne S Reiner
    120 Reiner
  2. Colin B Begg
    234 Begg
  3. Irene Orlow
    191 Orlow
  4. Klaus J Busam
    536 Busam
  5. Pampa Roy
    32 Roy
  6. Himali S Patel
    8 Patel