基质金属蛋白酶基因多态性与肺癌易感性的相关性研究

发布时间：2018-03-07 23:03

本文选题：MMPs　切入点：单核苷酸多态性　出处：《湖南工业大学》2017年硕士论文　论文类型：学位论文

【摘要】：肺癌是目前全球范围内最常见的恶性肿瘤之一,发病率和死亡率均呈上升趋势。烟草等吸入性致癌物是诱发肺癌的主要因素,但近年研究表明肺癌发病与遗传因素关系密切。单核苷酸多态性(SNP)是人类基因组最常见可遗传变异的一种。研究表明,基质金属蛋白酶(MMPs)是一类依赖于Zn2+高度保守的蛋白水解酶家族,有效降解细胞外基质和细胞基底膜成分。MMPs主要在转录水平调节基因表达,与肿瘤的侵袭和转移密切相关。本文旨在研究湖南地区人群MMP9、MMP13基因SNP及其联合作用以及MMP7基因SNP与肺癌遗传易感性和临床病理学参数的相关性。主要研究内容如下:(1)采用病例-对照法,对湖南地区182例肺癌患者和169例健康对照人群进行分析。记录研究对象的个人资料和临床病理学参数。使用DNA抽提试剂盒提取DNA,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法和直接测序法分析MMP9-1562C/T基因SNP与肺癌遗传易感性的相关性,所有数据由SPSS软件处理。结果表明,吸烟是肺癌发病的危险因子,且存在显著差异性(P=0.001,χ2=17.33)。Logistic回归分析显示,与MMP9-1562CT基因型相比,CC基因型能增加肺癌发病风险(OR=2.39,95%CI=1.45-3.92)。MMP9基因SNP与肺癌临床病理学参数没有相关性。(2)采用同样方法,分析182例肺癌患者和215例健康人群的MMP13-77A/G基因SNP与肺癌发病风险的相关性。结果表明,吸烟能增加肺癌发病风险(OR=0.00,χ2=27.13)。MMP13-77AA基因型相比于GG基因型是肺癌的保护因子(OR=0.53,95%CI=0.29-0.98)。MMP13基因SNP与肺癌临床病理学参数无明显相关性。MMP9 CC基因型与MMP13 GG基因型的联合作用能显著增加肺癌发病风险(OR=4.39,95%CI=2.08-9.26)。(3)对260例肺癌患者和219例对照人群MMP7-181A/G基因SNP与肺癌相关性的研究发现,吸烟能使肺癌发病风险增加(OR=0.00,χ2=26.51)。MMP7 AG基因型是肺癌易感因子,约是AA基因型的1.75倍(OR=1.75,95%CI=1.45-2.69)。MMP7基因SNP与肺癌临床病理学参数无相关性。
[Abstract]:Lung cancer is one of the most common malignant tumors in the world at present. The morbidity and mortality of lung cancer are on the rise. Inhaled carcinogens such as tobacco are the main factors inducing lung cancer. However, recent studies have shown that lung cancer is closely related to genetic factors. SNPs are one of the most common genetic variations in the human genome. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that are highly conserved by Zn2 and effectively degrade extracellular matrix and cell basement membrane components. MMPs mainly regulate gene expression at the transcriptional level. The purpose of this study was to study the association of MMP9 MMP13 gene SNP and its association with lung cancer susceptibility and clinicopathological parameters in Hunan province. The main contents of this study are as follows:. Using a case-control method, 182 lung cancer patients and 169 healthy controls in Hunan were analyzed. Personal data and clinicopathological parameters of the subjects were recorded. DNA extraction kit was used to extract DNA and polymerase chain reaction-restriction fragment was used. The relationship between MMP9-1562C/T gene SNP and genetic susceptibility to lung cancer was analyzed by PCR-RFLP and direct sequencing. All the data were processed by SPSS software. The results showed that smoking was the risk factor of lung cancer, and there was significant difference (P < 0.001). Compared with the MMP9-1562CT genotype, the CC genotype could increase the risk of lung cancer. The same method was used. There was no correlation between SNP and clinicopathological parameters of lung cancer. The relationship between MMP13-77A/G gene SNP and the risk of lung cancer was analyzed in 182 patients with lung cancer and 215 healthy controls. Smoking could increase the risk of lung cancer. Compared with the GG genotype, there was no significant correlation between the SNP of ORG gene 0.29-0.98 and the clinicopathological parameters of lung cancer. The combined effect of MMP9 CC genotype and MMP13 GG genotype could be significantly increased. The association between MMP7-181A/G gene SNP and lung cancer was studied in 260 patients with lung cancer and 219 controls. Smoking can increase the risk of lung cancer. 蠂 2 + 26.51U. MMP7 AG genotype is the susceptible factor of lung cancer, and 1.75 times as much as AA genotype. There is no correlation between the SNP of 1.45-2.69 ~ + .MMP7 gene and the clinicopathological parameters of lung cancer.
【学位授予单位】：湖南工业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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