Inherited variation at MC1R and histological characteristics of primary melanoma. Academic Article uri icon

Overview

abstract

  • Variation in the melanocortin-1receptor (MC1R) gene is associated with pigmentary phenotypes and risk of malignant melanoma. Few studies have reported on MC1R variation with respect to tumor characteristics, especially clinically important prognostic features. We examined associations between MC1R variants and histopathological melanoma characteristics. Study participants were enrolled from nine geographic regions in Australia, Canada, Italy and the United States and were genotyped for MC1R variants classified as high-risk [R] (D84E, R142H, R151C, R160W, and D294H, all nonsense and insertion/deletion) or low-risk [r] (all other nonsynonymous) variants. Tissue was available for 2,160 white participants of the Genes, Environment and Melanoma (GEM) Study with a first incident primary melanoma diagnosis, and underwent centralized pathologic review. No statistically significant associations were observed between MC1R variants and AJCC established prognostic tumor characteristics: Breslow thickness, presence of mitoses or presence of ulceration. However, MC1R was significantly associated with anatomic site of melanoma (p = 0.002) and a positive association was observed between carriage of more than one [R] variant and melanomas arising on the arms (OR = 2.39; 95% CI: 1.40, 4.09). We also observed statistically significant differences between sun-sensitive and sun-resistant individuals with respect to associations between MC1R genotype and AJCC prognostic tumor characteristics. Our results suggest inherited variation in MC1R may play an influential role in anatomic site presentation of melanomas and may differ with respect to skin pigmentation phenotype.

authors

  • Taylor, Nicholas J
  • Busam, Klaus
  • From, Lynn
  • Groben, Pamela A
  • Anton-Culver, Hoda
  • Cust, Anne E
  • Begg, Colin B.
  • Dwyer, Terence
  • Gallagher, Richard P
  • Gruber, Stephen B
  • Orlow, Irene
  • Rosso, Stefano
  • Thomas, Nancy E
  • Zanetti, Roberto
  • Rebbeck, Timothy R
  • Berwick, Marianne
  • Kanetsky, Peter A

publication date

  • March 19, 2015

Research

keywords

  • Genetic Association Studies
  • Melanoma
  • Receptor, Melanocortin, Type 1
  • Skin Neoplasms

Identity

PubMed Central ID

  • PMC4366050

Scopus Document Identifier

  • 84925438676

Digital Object Identifier (DOI)

  • 10.1016/j.amjsurg.2011.06.048

PubMed ID

  • 25790105

Additional Document Info

volume

  • 10

issue

  • 3