Document Detail


Influence of loss of function MC1R variants in genetic susceptibility of familial melanoma in Spain.
MedLine Citation:
PMID:  20539244     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We explored the presence of germline alterations in CDK4 exon 2, CDKN2A and MC1R in a hospital-based study of 89 melanoma cases from 89 families with at least two members affected by cutaneous melanoma. A total of 30% of the melanoma kindreds studied were carriers of CDKN2A variants, and three of these variants were known predominant alleles that have been identified earlier in Mediterranean populations (p.G101W, p.V59G and c.358delG). We observed a higher frequency of nonsynonymous MC1R variants in these Spanish melanoma kindreds (72%) with respect to the general population (60%). We observed a higher frequency of nonsynonymous MC1R variants in this Spanish melanoma kindred (72%) respect to general population (60%). A new classification of MC1R variants based on their functional effects over melanocortin-1 receptor, including the dominant-negative effect of some of them in heterozygotes, suggested an association of loss of function MC1R variants and multiple primary melanoma cases from melanoma kindred (odds ratio: 6.07, 95% confidence interval: 1.35-27.20). This study proposes the relevance of loss of function MC1R variants in the risk of melanoma in multiple primary melanoma cases with family history from areas with low melanoma incidence rate.
Authors:
Carlos de Torre; Zaida Garcia-Casado; Jorge A Martínez-Escribano; Rafael Botella-Estrada; Jose Bañuls; Vicente Oliver; Pedro Mercader; Jose M Azaña; Javier Frias; Eduardo Nagore
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Melanoma research     Volume:  20     ISSN:  1473-5636     ISO Abbreviation:  Melanoma Res.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-08     Completed Date:  2010-10-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9109623     Medline TA:  Melanoma Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  342-8     Citation Subset:  IM    
Affiliation:
Research Unit, Hospital Universitario Virgen de la Arrixaca, Spain.
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MeSH Terms
Descriptor/Qualifier:
Cyclin-Dependent Kinase 4 / genetics
Exons
Genes, p16
Genetic Predisposition to Disease
Genetic Variation
Germ-Line Mutation
Humans
Melanoma / genetics*
Mutation
Phenotype
Polymorphism, Genetic
Receptor, Melanocortin, Type 1 / genetics*
Skin Neoplasms / genetics*
Spain
Chemical
Reg. No./Substance:
0/Receptor, Melanocortin, Type 1; EC 2.7.1.37/CDK4 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 4

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