Influence of interleukin-10 genetic polymorphism on... : Melanoma Research (original) (raw)

ORIGINAL ARTICLES

Influence of interleukin-10 genetic polymorphism on survival rates in melanoma patients with advanced disease

Alonso, Rebecaa b; Suarez, Anaa; Castro, Patriciac; Lacave, Angel J.b d; Gutierrez, Carmena c

aDepartment of Functional Biology, Area of Immunology

bInstituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Oviedo, Spain

Departments of cImmunology

dMedical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain

Sponsorship: This work was supported by Fondo de Investigacion Sanitaria (grant no. FIS-PI PI020481) and Fundacion para la Investigación Cientifica y Tecnológica (grant no. PB-MED01-13). RA was supported by FICYT DOC 02-01.

Correspondence and requests for reprints to Dr Carmen Gutierrez, Servicio de Inmunologia, Hospital Central de Asturias, Julian Claveria s/n, 33006 Oviedo, Spain

Tel: 34 985 106 130; fax: 34 985 106 195;

e-mail: [email protected]

Received 17 June 2004 Accepted (after revision) 22 October 2004

Abstract

Individual ability to produce interleukin-10 (IL-10) may be of relevance in the development and evolution of cutaneous melanoma, probably due to its immunosuppressor and anti-angiogenic properties. Single nucleotide polymorphisms at positions −1082 (G/A), −819 (C/T) and −592 (C/A) in the IL-10 gene promoter were analysed in 100 healthy individuals and 98 melanoma patients using fluorogenic hybridization-specific probes in a ‘real-time’ thermocycler. Polymorphic frequencies were correlated with various prognostic factors and overall survival. The frequency of IL-10 polymorphic variants was similar in patients and controls. However, high producer genotypes at the −1082 position were over-represented in males with an older age at diagnosis. The analysis of the promoter genotypes in patients stratified according to clinical prognostic factors did not show any associations, although a trend (not statistically significant) towards a prolonged survival in patients genotyped as high IL-10 producers was observed. In addition, the low producer −1082AA genotype was significantly associated with decreased survival in patients with advanced disease. Similarly, the presence of this genotype shortened the overall survival in males after recurrence or metastasis development. In conclusion, the frequency of genetic variants in the IL-10 gene promoter was not associated with melanoma appearance, but conditioned the age at diagnosis in males and the overall survival in patients with advanced disease.