ASSOCIATION OF FUNCTIONAL SINGLE NUCLEOTIDE POLYMORPHISMS IN MATRIX METALLOPROTEINASES (MMPS) GENES WITH COLORECTAL AND BREAST CANCER PROGRESSION
| Authors | |
|---|---|
| Year of publication | 2004 |
| Type | Article in Periodical |
| Magazine / Source | Physiol Res |
| MU Faculty or unit | |
| Citation | |
| Web | http://www.biomed.cas.cz/physiolres/pdf/2004/53_47p.pdf |
| Field | Oncology and hematology |
| Keywords | cancer; MMPs; gene polymorphisms |
| Description | The degradation of the microenvironment of cancer cells, composed of extracellular matrix (ECM), plays an important role in tumor progression and development of metastases. The most of this degradation is mediated by matrix metalloproteinases. The increased levels of MMPs activity in tumor tissue were reported. Functional promoter single nucleotide polymorphisms (SNP) in MMP-1 and MMP-3 genes increase their transcription levels and consequently their enzymatic activity. An insertion of G at -1607 bp in MMP-1 promoter creates an Ets transcription factor family binding site and thus increases MMP-1 transcription. A deletion of A at -1171 bp increases MMP-3 transcription. These polymorphisms probably play an important role in tumor progression and metastasis. Recently, several studies reported associations of these polymorphisms with breast, colorectal, lung and renal carcinomas. Thus we have genotyped 150 patients with colorectal carcinoma and 164 patients with breast cancer for above mentioned SNPs and analyzed allelic frequencies in subgroups with and without metastases. Our results show that there is a weak association between 5A allele and metastases development in colorectal cancer patients (p=0.04375). Since both MMP genes are located in chromosome 11 we have examined their linkage disequilibrium by chi-square test. 1G allele of MMP-1 promoter is closely linked with 5A allele of MMP-3 promoter (p<0,01). The results suggest the role of studied polymorphisms in metastases development is unequivocal. |
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