MC1R variants increase risk of melanomas harboring BRAF mutations
Graduate School of Biomedical Sciences; Department of Dermatology; Department of Molecular Genetics and Microbiology
Medical Subject Headings
Adolescent; Adult; Aged; Aged, 80 and over; Female; Genetic Predisposition to Disease; *Genetic Variation; Hair Color; Heterozygote; Humans; Male; Melanoma; Middle Aged; *Mutation; Neoplasms, Multiple Primary; Nevus; Proto-Oncogene Proteins B-raf; Receptor, Melanocortin, Type 1; Skin Neoplasms; Sunlight
Life Sciences | Medicine and Health Sciences
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.
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Citation: J Invest Dermatol. 2008 Oct;128(10):2485-90. Epub 2008 Mar 27. Link to article on publisher's site
DOI of Published Version
The Journal of investigative dermatology [corrected to Fargnoli, Maria Concetta]
Fargnoli, Maria Concetia; Pike, Kris; Pfeiffer, Ruth M.; Tsang, Shirley; Rozenblum, Ester; Munroe, David; Golubeva, Yelena; Calista, Donato; Seidenari, Stefania; Massi, Daniela; Carli, Paolo; Bauer, Juergen; Elder, David E.; Bastian, Boris C.; Peris, Ketty; and Landi, Maria T., "MC1R variants increase risk of melanomas harboring BRAF mutations" (2008). GSBS Student Publications. 1471.