| Abstract [eng] |
Carcinoma of bladder is one of the leading causes of death. Successful treatment of bladder cancer depends on the early detection and specific diagnostic approaches. In the present study, microsatellite instability (MSI) and matrix metalloproteinases (MMPs) polymorphism has been evaluated as a prognostic marker in patients with bladder cancer. Microsatellites are short sequences of 1-6 bp repeated in tandem throughout the genome, and because of their polymorphic nature, they have been widely used as genetic markers. The detection of genomic instability is an important step in molecular analysis of tumourgenesis. Analysis of highly polymorphic microsatellite loci not only provides information about microsatellite instability but also allows the detection of allelic deletion in tumour cells. Ample evidence indicates that MMPs also contribute in multiple ways to all stages of malignant progression, including tumor invasion, blood vessel penetration, metastases and tumor angiogenesis. A number of DNA polymorphisms in the MMP genes are associated with differences in MMP activity. Five or six adenosines (5A or 6A) single nucleotide polymorphism (SNP) at position -1171 in the MMP-3 promoter and a cytosine (C) - thymidine (T) single nucleotide polymorphism (SNP) at position -1562 in the MMP-9 promoter are reported to affect expression of these genes. However, the relationship between the polymorphism and susceptibility of the cancer remains ambiguous. The aim of this study was to examine the specific microsatellite markers and to determine the prevalence of a single nucleotide polymorphism (-1171 5A/6A) in the MMP-3 and (-1562 C/T) in the MMP-9 gene promoters, and evaluate these polymorphisms on clinical stage. PCR and capillary electrophoresis method was used to determine microsatellite status in 29 bladder cancer patients tumours and blood. PCR-RFLP method was used for MMP-3 and MMP-9 polymorphisms identifications. Significant association was found between tumour differentiation degree and analyzed polymorphisms in bladder cancer. |
