人类MMP3基因5'端转录调控区rs522616单核苷酸多态性与食管鳞癌遗传易感性的关系

Association of the rs522616 single nucleotide polymorphism in the 5'-transcriptional regulatory region of the human matrix metalloproteinase-3 gene with susceptibility to esophageal squamous cell carcinoma

目的:探寻人类基质金属蛋白酶3(matrix metalloproteinase 3,MMP3)基因单核苷酸多态性与食管鳞癌易感性的关系.方法:选择mmp3基因上游转录调控区-774位rs522616(A/G)位点为研究对象.利用蛋白酶K法提取人类外周血基因组DNA;采用PCR-RFLP的方法对外周血标本进行基因分型,分别对河南食管鳞癌散发病例、湖北食管鳞癌散发病例以及两地正常人、河南高发区移民的不同人群组合做病例-对照分析.运用SPSS软件(version17.0)对基因分型结果进行数据统计分析.结果:rs522616(A/G)等位基因有AA、AG、GG3种分型.湖北正常人群与河南散发人群在AA基因型频率上有显著差异(P=0.001,OR=4.249),在GG基因型频率有差异(P=0.003,OR=4.424);湖北正常人群与河南高发区移民在GG基因型频率上有差异(P=0.019,OR=0.488);湖北散发人群和河南散发人群在GG基因型频率上有差异(P=0.04,OR=1.926)、在AA基因型频率上有显著差异(P=0.001,OR=0.282);河南散发患者与河南正常人群有在AA基因型频率上有显著差异(P=0.001,OR=1.893)、在AG基因型频率上有差异(P=0.049,OR=1.652);河南高发区移民与河南散发患者在AA基因型频率上有显著差异(P=0.005,OR=2.311)、在AG基因型频率上有差异(P=0.024,OR=0.549);另外,湖北人群(湖北正常人群+湖北散发患者)与河南人群(河南正常人群+河南散发患者)在AA基因型频率有显著差异(P=0.001,OR=2.553);湖北与河南两地的正常人群与两地的散发病例AA基因型频率有显著差异(P=0.001,OR=2.152).结论:MMP3基因上游转录调控区rs522616单核苷多态性与人群食管鳞癌的遗传易感性有明显相关.

AIM： To investigate the genetic association between a single nucleotide polymorphism [-774 rs522616 （A/G）] in the matrix metalloproteinase 3 gene and susceptibility to esophageal cancer. METHODS： Genomic DNA was extracted from peripheral blood samples of sporadic cases of esophageal cancer in both Henan and Hubei, immigrants from an area of high incidence in Henan, and healthy controls in both Henan and Hubei. The rs522616 polymorphism was genotyped using PCR-RFLP, and genotyping results were analyzed using SPSS software. RESULTS： The rs522616 （A/G） allele has three genotypes： GG, GA and AA. There were significant differences between healthy controls in Hubei and sporadic cases of esophageal cancer in Henan in genotypes GG and AA （P = 0.001, 0.003; OR = 4.249, 4.424）; immigrants from an area of high incidence in Henan and healthy controls in genotype GG （P = 0.019, OR = 0.488）; sporadic cases of esophageal cancer in Henan and sporadic cases of esophageal cancer in Hubei in genotypes GG and AA （P = 0.04, 0.001; OR = 1.926, 0.282）; immigrants from an area of high incidence in Henan and sporadic cases of esophageal cancer in Henan in genotypes AG and AA （P = 0.024, 0.005; OR = 0.549, 2.311）; and sporadic cases of esophageal cancer in Henan and healthy controls in Henan in genotypes AG and AA （P = 0.049, 0.005; OR = 1.65, 2.311）. Moreover, there were significant differences between people in Hubei and those in Henan in genotype AA （P = 0.001, OR = 2.553）, and between healthy controls （including healthy controls both in Henan and Hubei） and sporadic cases of esophageal cancer （including sporadic cases of esophageal cancer both in Henan and Hubei） in genotype AA （P = 0.001, OR = 2.152）. CONCLUSION： The single nucleotide polymorphism rs522616 in the transcriptional regulatory region of the human matrix metalloproteinase 3 gene is apparently associated with susceptibility to esophageal cancer.