Polymorphisms in the CD28-CTLA4-ICOS genes: role in malignant melanoma susceptibility and prognosisReportar como inadecuado

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Cancer Immunology, Immunotherapy

, 59:303

First Online: 12 August 2009Received: 08 June 2009Accepted: 28 July 2009


The appearance of vitiligo and spontaneous regression of the primary lesion in melanoma patients illustrate a relationship between tumor immunity and autoimmunity. T lymphocytes play a major role both in tumor immunity and autoimmunity. CD28, Cytotoxic T lymphocyte antigen 4 CTLA4 and inducible costimulator ICOS molecules are important secondary signal molecules in the T lymphocyte activation. Single nucleotide polymorphisms SNPs in the CD28-CTLA4-ICOS gene region were reported to be associated with several autoimmune diseases including, type-1 diabetes, SLE, autoimmune thyroid diseases and celiac disease. In this study, we investigated the association of SNPs in the CD28, CTLA4 and ICOS genes with the risk of melanoma. We also assessed the prognostic effect of the different polymorphisms in melanoma patients. Twenty-four tagging SNPs across the three genes and four additional SNPs were genotyped in a cohort of 763 German melanoma patients and 734 healthy German controls. Influence on prognosis was determined in 587 melanoma cases belonging to stage I or II of the disease. In general, no differences in genotype or allele frequencies were detected between melanoma patients and controls. However, the variant alleles for two polymorphisms in the CD28 gene were differentially distributed in cases and controls. Similarly no association of any polymorphism with prognosis, except for the rs3181098 polymorphism in the CD28 gene, was observed. In addition, individuals with AA genotype for rs11571323 polymorphism in the ICOS gene showed reduced overall survival. However, keeping in view the correction for multiple hypothesis testing our results suggest that the polymorphisms in the CD28, CTLA4 and ICOS genes at least do not modulate risk of melanoma and nor do those influence the disease prognosis in the investigated population.

KeywordsMelanoma Polymorphism CD28-CTLA4-ICOS Susceptibility Prognosis Electronic supplementary materialThe online version of this article doi:10.1007-s00262-009-0751-2 contains supplementary material, which is available to authorized users.

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Autor: Marna G. Bouwhuis - Andreas Gast - Adina Figl - Alexander M. M. Eggermont - Kari Hemminki - Dirk Schadendorf - Rajiv Kum

Fuente: https://link.springer.com/

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