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

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.