title: MC1R, ASIP, TYR, and TYRP1 gene variants in a population-based series of multiple primary melanomas.
abstract: Allelic variants of the low-penetrance melanoma gene MC1R increase the risk of both melanoma and non-melanoma skin cancer. Common variants of the genes ASIP, TYR, and TYRP1, which regulate the melanogenic pathway, have also been shown to associate with melanoma. In this population-based study, we investigated SNPs of MC1R, ASIP, TYR, and TYRP1 as risk factors for development of multiple primary melanomas (MPM) in 388 Norwegian cases. The MPM patients had a significantly higher likelihood of carrying any MC1R variant than the control group of 420 blood donors [86.8 vs. 78.3%, OR = 1.73, and confidence intervals (CI) 1.18-2.52]. When MC1R variants were analyzed individually, Asp84Glu and Arg151Cys were significantly more frequent among the MPM cases than among the controls (OR = 5.77, CI 1.97-16.90, and OR = 1.80, CI 1.36-2.37, respectively). In addition, there was an allele dose-dependent increase in MPM risk for carriers of red hair color (RHC) MC1R variants. The AH haplotype of ASIP was also a significant risk factor for MPM development (OR = 1.72 and CI 1.12-2.49), whereas no association was observed for previously reported risk variants of the TYR and TYRP1 genes. In summary, by using a population-based material of high-risk melanoma cases, we demonstrate a significant effect of both MC1R RHC variants and an ASIP haplotype, but could not replicate an association with postulated risk SNPs of TYR and TYRP1.
authors.affiliation: Department of Dermatology, Oslo University Hospital, Rikshospitalet, N-0027 Oslo, Norway. per.helsing@rikshospitalet.no
authors.forename: Per
authors.initials: P
authors.lastname: Helsing
authors.forename: Dag A
authors.initials: DA
authors.lastname: Nymoen
authors.forename: Helge
authors.initials: H
authors.lastname: Rootwelt
authors.forename: Mari
authors.initials: M
authors.lastname: Vårdal
authors.forename: Lars A
authors.initials: LA
authors.lastname: Akslen
authors.forename: Anders
authors.initials: A
authors.lastname: Molven
authors.forename: Per A
authors.initials: PA
authors.lastname: Andresen
mesh_terms: D000328:Adult; D000368:Aged; D054366:Agouti Signaling Protein / Q000235:genetics*; D005260:Female; D006200:Hair Color / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000235:genetics*; D009664:Norway / Q000453:epidemiology; D016017:Odds Ratio; D010088:Oxidoreductases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics*
chemical_list: C515182:ASIP protein, human; D054366:Agouti Signaling Protein; D008562:Membrane Glycoproteins; D044102:Receptor, Melanocortin, Type 1; D010088:Oxidoreductases; C489799:TYRP1 protein, human; D014442:Monophenol Monooxygenase