Melanocortin receptor 1 variants and melanoma risk: a study of 2 European populations.

Full 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.

Author information

Author/s: Scherer, Dominique (D); Nagore, Eduardo (E); Bermejo, Justo Lorenzo (JL); Figl, Adina (A); Botella-Estrada, Rafael (R); Thirumaran, Ranjit Kumar (RK); Angelini, Sabrina (S); Hemminki, Kari (K); Schadendorf, Dirk (D); Kumar, Rajiv (R);

Affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, 69120 Heidelberg, Germany. d.scherer(-atsign-)dkfz.de

Journal and publication information

Publication Type: Comparative Study; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Oct; vol 125 (issue 8) : pp 1868-75

Dates: Created 2009/08/26; Completed 2009/09/21;

PMID: 19585506, status: MEDLINE (last retrieval date: 9/21/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.