1. ¹Department of Dermatology, University of Athens Medical School, Andreas Sygros Hospital, Athens, Greece
2. ²Medical Genetics, University of Athens Medical School, Agia Sophia Children's Hospital, Athens, Greece
3. ³Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece
4. ⁴Department of Internal Medicine/Oncology, University of Athens Medical School, Laikon Hospital, Athens, Greece
5. ⁵Department of Plastic Surgery and Microsurgery, Gennimatas General Hospital, Athens, Greece

Correspondence: Dr Alexander J. Stratigos, Department of Dermatology, University of Athens, Andreas Sygros Hospital, 5 Dragoumi Street, Athens 10671, Greece. E-mail: alstrat@hol.gr

Received 7 December 2005; Revised 5 February 2006; Accepted 21 February 2006; Published online 6 April 2006.

Abstract

Individuals with melanocortin 1 receptor (MC1R) gene variants have been shown to carry an increased risk for the development of melanoma. In this study, we investigated the relationship of MC1R gene variants and the risk of melanoma in 123 melanoma patients and 155 control subjects from Greece. The entire MC1R gene was sequenced for polymorphisms and the results were correlated with host factors and pigmentary characteristics. MC1R polymorphisms were present in 59.4% of melanoma patients compared to 37.5% of controls, yielding an odds ratio (OR) of 2.43 (95% confidence interval (CI)=1.50–3.96, P<0.001) for melanoma among MC1R carriers. The risk of melanoma was enhanced in individuals carrying multiple variant alleles (OR=6.97; 95% CI=1.86–26.12, P=0.004). Only the Val60Leu, Arg142His, and Arg151Cys variants were significantly associated with melanoma risk. In stratified analysis, the risk of melanoma among MC1R carriers was not influenced by skin phototype, skin color, or hair color. No association was found between MC1R genotype and the age of onset of melanoma, the tumor location, or the tumor thickness. In conclusion, MC1R polymorphisms are a predisposing factor of melanoma in a southern European population with a relatively low incidence of the disease.