A single nucleotide polymorphism in the MMP-1 promoter is correlated with histological differentiation of gastric cancer
- 163 Downloads
Matrix metalloproteinase-1 (MMP-1) plays a key role in cancer invasion and metastasis by degradation of extracellular matrix (ECM) and basement membrane barriers. The 1G/2G single nucleotide polymorphism (SNP) in the MMP-1 promoter at position –1607 bp has been reported to affect the transcriptional activity. In the light of these findings, we investigated whether this SNP in the MMP-1 promoter is associated with the development, differentiation, and progression of gastric cancer.
The 215 gastric cancer patients and 166 controls were used in this study. The SNP of the MMP-1 promoter was analyzed by PCR-RFLP and sequencing. The genotype frequency was compared between cases and controls, and the association with clinicopathological parameters among cases was studied.
The frequency of 1G/2G genotypes in gastric cancer patients was similar to those in controls (p=0.57). The degree of tumor invasion, the presence of lymph node metastasis, and clinical stage showed no significant association with the SNP. On the other hand, we found a significant association with histological differentiation and gender among gastric cancer patients (p<0.05, respectively).
The presence of 2G allele in the MMP-1 promoter did not enhance the risk of gastric cancer; however, it may be involved in differentiation of gastric cancer.
KeywordsSNP MMP-1 Gastric cancer
- Hewitt RE, Leach IH, Powe DG, Clark IM, Cawston TE, Turner DR (1991) Distribution of collagenase and tissue inhibitor of metalloproteinases (TIMP) in colorectal tumours. Int. J Cancer 49:666–672Google Scholar
- Ito R, Kitadai Y, Kyo E, Yokozaki H, Yasui W, Yamashita U, Nikai H, Tahara E (1993) Interleukin 1 alpha acts as an autocrine growth stimulator for human gastric carcinoma cells. Cancer Res 53:4102–4106Google Scholar
- Lauren P (1965) The two histological main types of gastric carcinoma. Diffuse and so-called intestinal type carcinoma: an attempt at histological classification. Acta Pathol Microbiol Scand 64:31–49Google Scholar
- McDonnel S, Matrisian LM (1991) Stromelysin in tumor progression and invasion. Cancer Metastasis Rev 9:305–319Google Scholar
- Otani Y, Kubota T, Sakurai Y, Igarashi N, Yokoyama T, Kimata M, Wada N, Kameyama K, Kumai K, Okada Y, Kitajima M (1999) Expression of matrix metalloproteinases in gastric carcinoma and possibility of clinical application of matrix metalloproteinase inhibitor in vivo. Ann N Y Acad Sci 30:541–543Google Scholar
- Rutter JL, Mitchell TI, Buttice G, Meyers J, Gusella JF, Ozelius LJ, Brinckerhoff CE (1998) A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter creates an Ets binding site and augments transcription. Cancer Res 58:321–5325Google Scholar
- Sobin LH, Wittekind CH (eds) (2002) TNM classification of malignant tumors, 6th edn. Wiley-Liss, New York, pp 65–68Google Scholar
- Stelzner S, Emmrich P (1997) The mixed type in Lauren’s classification of gastric carcinoma. Histologic description and biologic behavior. Gen Diagn Pathol143:39–48Google Scholar