Clinicopathological significance of MMP-2 and TIMP-2 genotypes in gastric cancer

Eur J Cancer. 2007 Mar;43(4):799-808. doi: 10.1016/j.ejca.2006.10.022. Epub 2007 Jan 22.

Abstract

Aims: Single nucleotide polymorphisms in matrix metalloproteinase-2 (MMP-2) -1306 C/T and tissue inhibitor of metalloproteinase-2 (TIMP-2) -418 G/C abolish the Sp-1 binding site and down-regulate expression of these genes. We aim to elucidate the role of MMP-2 and TIMP-2 in clinicopathological manifestations of gastric cancer.

Methods: We enrolled 240 gastric cancer patients and 283 controls. DNA was extracted from peripheral blood leucocytes. MMP-2 and TIMP-2 genotypes were analysed by PCR-direct sequencing and PCR-RFLP method, respectively.

Results: MMP-2 and TIMP-2 genotypes were not associated with gastric cancer development. However, patients with MMP-2 -1306 C/C genotype showed higher risk of lymphatic invasion (odds ratio (OR)=2.77, p=0.01) and venous invasion (OR=2.93, p=0.012). TIMP-2 G/G genotype was associated with serosal invasion (OR=1.89, p=0.009), lymph node metastasis (OR=2.19, p=0.021), lymphatic invasion (OR=2.87, p=0.016) and venous invasion (OR=2.65, p=0.033).

Conclusion: Our results suggest MMP-2 and TIMP-2 genotypes play a crucial role in gastric cancer invasion, but not with development of gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Genotype
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / genetics*
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Neoplasm, Residual / genetics
  • Neoplasm, Residual / mortality
  • Neoplasm, Residual / pathology
  • Risk Factors
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Survival Analysis
  • Tissue Inhibitor of Metalloproteinase-2 / genetics*

Substances

  • Neoplasm Proteins
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 2