497 FOXP3 and CTLA-4 genetic variants influence on the susceptibility and clinical course of basal cell carcinoma

Abstract

The pathogenesis of basal cell carcinoma (BCC) is multifactorial and not fully elucidated. Previous studies showed, that behaviour of the tumour may be influenced by immune system and identified CD4+CD25+FoxP3+ regulatory T cells (Tregs) as a dominant immune cells in BCC microenvironment. The function and development of Tregs is regulated by FOXP3 encoding transcription factor, Forkhead box P3 (FoxP3). FoxP3 regulates transcription of many genes, including up-regulation of cytotoxic lymphocyte-associated antigen-4 gene (CTLA-4). Expressed on Tregs, CTLA-4 interacts with antigen-presenting cells to inhibit T-cell activation. The aim of the study was to investigate the role of two polymorphisms (rs3761548 i rs2232365) of FOXP3 and CLTA-4 polymorphism (rs5742909) in BCC patients from northern Poland. We analyzed 280 unrelated patients with BCC and of mean age 70.93±11.53(70.54±12.55 women, 71.38±10.26 men) and 200 healthy, unrelated age- and sex-matched volunteers. The polymorphisms were analyzed using polymerase chain reaction with sequence-specific primers (SSP-PCR). The differences in the occurrence of BCC between genotypes and alleles of the analyzed polymorphisms were not statistically significant. In the studied group the presence of CC genotype in CTLA-4 rs5742909 polymorphism was statistically more frequent in patients with multiple BCCs. In concusion, the analyzed FOXP3 and CLTA-4 polymorphisms do not influence the BCC susceptibility. CTLA-4 rs5742909 polymorphism may influence the susceptibility to multiple BCCs.