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

JURAJDA, Michal a Jiří VÁCHA. ASSOCIATION OF FUNCTIONAL SINGLE NUCLEOTIDE POLYMORPHISMS IN MATRIX METALLOPROTEINASES (MMPS) GENES WITH COLORECTAL AND BREAST CANCER PROGRESSION. Physiol Res. Praha: Institute of Physiology, Academy of Sci, roč. 53/2004, č. 5, s. 51P, 1 s. ISSN 0862-8408. 2004.

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

• Originální 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
• WWW: URL
• Impakt faktor: Impact factor: 1.140
• Kód RIV: RIV/00216224:14110/04:00010701
• Organizační jednotka: Lékařská fakulta
• Klíčová slova anglicky: cancer; MMPs; gene polymorphisms
• Štítky: cancer, gene polymorphisms, MMPs

Anotace

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.

Anotace 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