Association Study Of MMP-2 And TIMP-2 And Its Single Nucleotide Polymorphisms With Gastric Carcinoma

【Objective】Gastric cancer is one of the most common malignancies. Because the matrix metalloproteinases play important roles in all stages of cancer initiation and development, they have been focused as a group of important candidate genes in recent years.The relationship between MMP-2,TIMP-2 and cancer is particularly interesting. With the molecularbiological development, studies have found that some single nucleotide polymorphisms (SNPs) of MMP-2 and TIMP-2 genes. They may influence the transcription of the gene and expression of protein and relate to occurrence and development of some tumor. This study was designed to investigate the association between single nucleotide polymorphisms (SNPs) in MMP-2 and TIMP-2 genes and the risk of gastric cancer. By this way, we hope to offer some evidences for the prevention and therapy of gastric cancer at molecular level.【Methods】1. In the first part of our study, Archival tissues from 91 patients with gastric cancer were retrieved. Matched samples including adjacent normal gastric tissues, primary tumor and metastasis lymph node tissues were investigated immunohistochemically.2. This case-control study included 479 gastric cancer patients(paraffin specimens) and 469 healthy control(peripheral blood). DNA was extracted by genome TIANGEN extraction kit and lots of whole blood genomic DNA extraction kit (solution type). MMP-2 rs243865 C>T,rs2241145 G>C,rs7201 A>C and TIMP-2 rs4789933 A>G,rs1531796 C>T,rs2277698 G>A SNPs were genotyped by Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS). Statistical analysis was performed using SPSS11.5 software package.【Results】1. The positive rates of MMP-2 and TIMP-2 protein in primary tumor were obviously higher than adjacent normal gastric tissues (P<0.05).2. The genotype and allele distributions of TIMP-2 rs2277698 G>A were significantly different in the gastric cancer group to the control group (P=0.03). Compared with the AA genotypes, the G genotype(GG + GA)significantly increased the risk of gastric cancer(OR=1.94,95 (%) CI:1.18-3.20; P=0.008).3. TIMP-2 rs2277698 G>A carrying G(GG+ AG) genotype is 3.4 times as carrying AA genotype in tumor infiltration(OR=3.4,95 (%) CI:1.5-7.8; P=0.002).4. TIMP-2 rs1531796 C>T carrying C(CC + CT)genotype is 4.9 times as carrying T genotype in lymph node metastasis (OR=4.9,95 (%) CI:1.6-15.3; P=0.002).【Conclusions】1.The expression of MMP-2 and TIMP-2 is closely related to the invasion of gastric cancer.Combined analyses of the expression of MMP-2 and TIMP-2 could be helpful in the evaluation of the clinicopathologic features and prognosis of patients with gastric cancer.2.TIMP-2 rs2277698 G>A carrying G(GG+ AG) genotype may significantly increased the risk of developing gastric cancer and may significantly associated with infiltration depth.3.TIMP-2 rs1531796 C>T carrying C genotype may increased the risk of lymph node metastasis in gastric cancer patients.