J 2004

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

JURAJDA, Michal a Jiří VÁCHA

Základní údaje

Originální název

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

Název česky

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

Autoři

JURAJDA, Michal (203 Česká republika, garant) a Jiří VÁCHA (203 Česká republika)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 1.140

Kód RIV

RIV/00216224:14110/04:00010701

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

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

Anotace

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.

Česky

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.

Návaznosti

MSM 141100002, záměr
Název: Molekulární patofyziologie multigenních chorob
Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Molekulární patofyziologie multigenních chorob