title: MC1R variants increase risk of melanomas harboring BRAF mutations.
abstract: Melanocortin-1 receptor (MC1R) variants have been associated with BRAF (v-raf murine sarcoma viral oncogene homolog B1) mutations in non-CSD (chronic solar-damaged) melanomas in an Italian and an American population. We studied an independent Italian population of 330 subjects (165 melanoma patients and 165 controls) to verify and estimate the magnitude of this association and to explore possible effect modifiers. We sequenced MC1R in all subjects and exon 15 of BRAF in 92/165 melanoma patients. Patients with MC1R variants had a high risk of carrying BRAF mutations in melanomas (odds ratio (OR)=7.0, 95% confidence interval (CI)=2.1-23.8) that increased with the number of MC1R variants and variants associated with red hair color. Combining these subjects with the originally reported Italian population (513 subjects overall), MC1R variant carriers had a 5- to 15-fold increased risk of BRAF-mutant melanomas based on carrying one or two variants (P<0.0001, test for trend), and regardless of signs of chronic solar damage. In contrast, no association with BRAF-negative melanomas was found (OR=1.0, 95% CI=0.6-1.6). No characteristics of subjects or melanomas, including age, nevus count, pigmentation, and melanoma thickness or location on chronically or intermittently sun-exposed body sites, substantially modified this association, although results could be affected by the small numbers in some categories. This study confirms that the known MC1R-melanoma risk association is confined to subjects whose melanomas harbor BRAF mutations.
authors: Department of Dermatology, University of L'Aquila, L'Aquila, Italy.
authors: Maria Concetta
authors: MC
authors: Fargnoli
authors: Maria Concetia
authors: MC
authors: Fargnoli
authors: Kris
authors: K
authors: Pike
authors: Ruth M
authors: RM
authors: Pfeiffer
authors: Shirley
authors: S
authors: Tsang
authors: Ester
authors: E
authors: Rozenblum
authors: David J
authors: DJ
authors: Munroe
authors: Yelena
authors: Y
authors: Golubeva
authors: Donato
authors: D
authors: Calista
authors: Stefania
authors: S
authors: Seidenari
authors: Daniela
authors: D
authors: Massi
authors: Paolo
authors: P
authors: Carli
authors: Juergen
authors: J
authors: Bauer
authors: David E
authors: DE
authors: Elder
authors: Boris C
authors: BC
authors: Bastian
authors: Ketty
authors: K
authors: Peris
authors: Maria T
authors: MT
authors: Landi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006200:Hair Color / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000473:pathology; D009506:Nevus / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D013472:Sunlight
chemical_list: D044102:Receptor, Melanocortin, Type 1; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf