基质金属蛋白酶(MMP)-2和-9功能性单核苷酸多态与胃癌

背景与目的：基质金属蛋白酶(matrix metalloproteinase,MMP)-2和-9在胃癌的发生和发展中起重要作用。本研究探讨这2个基因的功能性单核苷酸多态与胃癌发生风险的关系。方法：以聚合酶链反应和变性高压液相色谱以及限制性片段长度多态性分析方法,分别检测228个胃癌患者和774个正常对照者MMP-2-1306T/C和MMP-9-1562C/T多态的基因型;比较不同基因型与胃癌风险的关系,并以效应修饰模型分析基因-基因之间的交互作用。结果：与MMP-2-1306TT或CT基因型携带者比较,MMP-2-1306CC基因型携带者罹患胃癌的风险增加1．67倍(95％CI,1．17～2．38)。MMP-9-1562C/T多态单独与胃癌风险无关,但与MMP-2-1306T/C多态可能有基因-基因交互作用,因为携带MMP-2-1306CC和MMP-9-1562TT或CT基因型的个体,罹患胃癌的风险显著增高(似然比检验,P=0．02)。结论：MMP-2和MMP-9基因单核苷酸多态可能与胃癌的遗传易感性有关。

Association of functional polymorphisms in matrix metalloproteinase-2 (MMP-2) and MMP-9 genes with risk of gastric cancer in a Chinese population

BACKGROUND &OBJECTIVE: Matrix metalloproteinase 2 (MMP 2) and 9 (MMP 9) play important roles in the development of gastric cancer. This study was to investigate the association of functional polymorphisms in the MMP 2 and MMP 9 genes with risk of gastric cancer in a Chinese population.METHODS:MMP 2 -1306T/C,and MMP 9 -1562C/T polymorphisms in 228 paitents with gastric cancer, and 774 matched healthy controls were detected by polymerase chain reaction (PCR) based denaturing high performance liquid chromatography, and PCR based restriction fragment length polymorphism analysis. The adjusted odds ratios (ORs) and 95%confidence intervals (CIs) were calculated using unconditional logistic regression model. The effect modified model was used to evaluate the gene gene interaction.RESULTS: Subjects with the MMP 2 -1306CC genotype had an increased risk of developing gastric cancer compared with those with the MMP 2 -1306TT or CT genotype (adjusted OR, 1.67; 95%CI, 1.17-2.38). No significant association between MMP 9 -1562C/T polymorphism and risk of gastric cancer was observed. However, the polymorphisms in these 2 genes seem to display a gene gene interaction, with OR of 1.72 (95%CI, 1.07-2.78) for subjects carrying both MMP 2 -1306CC and MMP 9 -1562TT or CT genotypes compared with those carrying both MMP 2 -1306TT or CT and MMP 2 -1306T/C genotypes (likelihood ratio test, P=0.02). CONCLUSION: MMP 2 -1306T/C and MMP 9 -1562C/T polymorphisms may be associated with genetic susceptibility to gastric cancer.