MC1R variants increase risk of melanomas harboring BRAF mutations
Authors
Fargnoli, Maria ConcetiaPike, 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
Landi, Maria T.
UMass Chan Affiliations
Department of Molecular Genetics and MicrobiologyDepartment of Dermatology
Graduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2008-03-28Keywords
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; SunlightLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
J Invest Dermatol. 2008 Oct;128(10):2485-90. Epub 2008 Mar 27. Link to article on publisher's siteDOI
10.1038/jid.2008.67Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32920PubMed ID
18368129Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/jid.2008.67