title: MC1R germline variants confer risk for BRAF-mutant melanoma.
abstract: Germline variants in MC1R, the gene encoding the melanocortin-1 receptor, and sun exposure increase risk for melanoma in Caucasians. The majority of melanomas that occur on skin with little evidence of chronic sun-induced damage (non-CSD melanoma) have mutations in the BRAF oncogene, whereas in melanomas on skin with marked CSD (CSD melanoma) these mutations are less frequent. In two independent Caucasian populations, we show that MC1R variants are strongly associated with BRAF mutations in non-CSD melanomas. In this tumor subtype, the risk for melanoma associated with MC1R is due to an increase in risk of developing melanomas with BRAF mutations.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA. landim@mail.nih.gov
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Landi
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bauer
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.forename: David E
authors.initials: DE
authors.lastname: Elder
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hulley
authors.forename: Paola
authors.initials: P
authors.lastname: Minghetti
authors.forename: Donato
authors.initials: D
authors.lastname: Calista
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kanetsky
authors.forename: Daniel
authors.initials: D
authors.lastname: Pinkel
authors.forename: Boris C
authors.initials: BC
authors.lastname: Bastian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D018095:Germ-Line Mutation; D006801:Humans; D007558:Italy; D008297:Male; D008545:Melanoma / Q000145:classification / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012867:Skin / Q000473:pathology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D013472:Sunlight / Q000009:adverse effects*; D014481:United States
chemical_list: D044102:Receptor, Melanocortin, Type 1; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf