title: Melanocortin receptor 1 variants and melanoma risk: a study of 2 European populations.
abstract: Variation within the melanocortin receptor 1 (MC1R) gene, that influences phenotypic traits and susceptibility to melanoma, is abundant across the populations. We assessed and compared the risk of melanoma in 2 European populations, German and Spanish, by genotyping MC1R variants through direct DNA sequencing from 1,185 melanoma cases and 1,582 controls. The presence of any variant in both populations was associated with a significantly increased risk of melanoma (odds ratio OR = 1.67, 95% confidence interval CI 1.40-1.99). The population attributable fractions (PAF) associated with the MC1R variants in both populations was over 25%. However, the results showed a statistically significant (p < 0.0001) higher frequency of MC1R variants in the German (70%) than in the Spanish population (60%). The red-hair colour (RHC) variants, though associated with increased risk in both populations, were more common in the German than in the Spanish population (p < 0.0001). Interestingly, non-RHC variants increased the disease risk in the Spanish (OR = 1.60, 95% CI 1.20-2.14) but not in the German population (OR = 1.07, 95% CI 0.80-1.44). Although RHC variants explained a major proportion of the observed PAF in the German population, in the Spanish population the major contributor to the PAF was the non-RHC V60L variant. We also observed reduced historic linkage disequilibrium between the variants V92M and T314T in the gene in German melanoma cases. In conclusion, our data underscored the unambiguous importance of the MC1R variants towards the population burden of melanoma. However, the variants that are associated with the disease differ between the investigated populations.
authors: Division of Molecular Genetic Epidemiology, German Cancer Research Center, 69120 Heidelberg, Germany. d.scherer@dkfz.de
authors: Dominique
authors: D
authors: Scherer
authors: Eduardo
authors: E
authors: Nagore
authors: Justo Lorenzo
authors: JL
authors: Bermejo
authors: Adina
authors: A
authors: Figl
authors: Rafael
authors: R
authors: Botella-Estrada
authors: Ranjit Kumar
authors: RK
authors: Thirumaran
authors: Sabrina
authors: S
authors: Angelini
authors: Kari
authors: K
authors: Hemminki
authors: Dirk
authors: D
authors: Schadendorf
authors: Rajiv
authors: R
authors: Kumar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D005260:Female; D014644:Genetic Variation; D005828:Genetics, Population; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006200:Hair Color / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics*; D013030:Spain / Q000453:epidemiology; D055815:Young Adult
chemical_list: D044102:Receptor, Melanocortin, Type 1