J 2004

ASSOCIATION OF FUNCTIONAL SINGLE NUCLEOTIDE POLYMORPHISMS IN MATRIX METALLOPROTEINASES (MMPS) GENES WITH COLORECTAL AND BREAST CANCER PROGRESSION

JURAJDA, Michal and Jiří VÁCHA

Basic information

Original name

ASSOCIATION OF FUNCTIONAL SINGLE NUCLEOTIDE POLYMORPHISMS IN MATRIX METALLOPROTEINASES (MMPS) GENES WITH COLORECTAL AND BREAST CANCER PROGRESSION

Name in Czech

asociace funkčních SNP v genech matrixmetalloproteináz s progresí karcinomu kolorekta a prsu

Authors

JURAJDA, Michal (203 Czech Republic, guarantor) and Jiří VÁCHA (203 Czech Republic)

Edition

Physiol Res, Praha, Institute of Physiology, Academy of Sci, 2004, 0862-8408

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 1.140

RIV identification code

RIV/00216224:14110/04:00010701

Organization unit

Faculty of Medicine

Keywords in English

cancer; MMPs; gene polymorphisms
Změněno: 31/5/2005 11:00, MUDr. Michal Jurajda, Ph.D.

Abstract

V originále

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.

In Czech

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.

Links

MSM 141100002, plan (intention)
Name: Molekulární patofyziologie multigenních chorob
Investor: Ministry of Education, Youth and Sports of the CR, Molecular pathophysiology of multigene diseases