MC1R germline variants confer risk for BRAF-mutant melanoma.
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.
Landi
Maria Teresa
MT
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA. landim@mail.nih.gov
Bauer
Jürgen
J
Pfeiffer
Ruth M
RM
Elder
David E
DE
Hulley
Benjamin
B
Minghetti
Paola
P
Calista
Donato
D
Kanetsky
Peter A
PA
Pinkel
Daniel
D
Bastian
Boris C
BC
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
D044102:Receptor, Melanocortin, Type 1; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf