發(fā)布時(shí)間：2018-03-07 23:03

  本文選題：MMPs　切入點(diǎn)：單核苷酸多態(tài)性　出處：《湖南工業(yè)大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：肺癌是目前全球范圍內(nèi)最常見的惡性腫瘤之一,發(fā)病率和死亡率均呈上升趨勢(shì)。煙草等吸入性致癌物是誘發(fā)肺癌的主要因素,但近年研究表明肺癌發(fā)病與遺傳因素關(guān)系密切。單核苷酸多態(tài)性(SNP)是人類基因組最常見可遺傳變異的一種。研究表明,基質(zhì)金屬蛋白酶(MMPs)是一類依賴于Zn2+高度保守的蛋白水解酶家族,有效降解細(xì)胞外基質(zhì)和細(xì)胞基底膜成分。MMPs主要在轉(zhuǎn)錄水平調(diào)節(jié)基因表達(dá),與腫瘤的侵襲和轉(zhuǎn)移密切相關(guān)。本文旨在研究湖南地區(qū)人群MMP9、MMP13基因SNP及其聯(lián)合作用以及MMP7基因SNP與肺癌遺傳易感性和臨床病理學(xué)參數(shù)的相關(guān)性。主要研究?jī)?nèi)容如下:(1)采用病例-對(duì)照法,對(duì)湖南地區(qū)182例肺癌患者和169例健康對(duì)照人群進(jìn)行分析。記錄研究對(duì)象的個(gè)人資料和臨床病理學(xué)參數(shù)。使用DNA抽提試劑盒提取DNA,采用聚合酶鏈反應(yīng)-限制性片段長(zhǎng)度多態(tài)性(PCR-RFLP)方法和直接測(cè)序法分析MMP9-1562C/T基因SNP與肺癌遺傳易感性的相關(guān)性,所有數(shù)據(jù)由SPSS軟件處理。結(jié)果表明,吸煙是肺癌發(fā)病的危險(xiǎn)因子,且存在顯著差異性(P=0.001,χ2=17.33)。Logistic回歸分析顯示,與MMP9-1562CT基因型相比,CC基因型能增加肺癌發(fā)病風(fēng)險(xiǎn)(OR=2.39,95%CI=1.45-3.92)。MMP9基因SNP與肺癌臨床病理學(xué)參數(shù)沒有相關(guān)性。(2)采用同樣方法,分析182例肺癌患者和215例健康人群的MMP13-77A/G基因SNP與肺癌發(fā)病風(fēng)險(xiǎn)的相關(guān)性。結(jié)果表明,吸煙能增加肺癌發(fā)病風(fēng)險(xiǎn)(OR=0.00,χ2=27.13)。MMP13-77AA基因型相比于GG基因型是肺癌的保護(hù)因子(OR=0.53,95%CI=0.29-0.98)。MMP13基因SNP與肺癌臨床病理學(xué)參數(shù)無明顯相關(guān)性。MMP9 CC基因型與MMP13 GG基因型的聯(lián)合作用能顯著增加肺癌發(fā)病風(fēng)險(xiǎn)(OR=4.39,95%CI=2.08-9.26)。(3)對(duì)260例肺癌患者和219例對(duì)照人群MMP7-181A/G基因SNP與肺癌相關(guān)性的研究發(fā)現(xiàn),吸煙能使肺癌發(fā)病風(fēng)險(xiǎn)增加(OR=0.00,χ2=26.51)。MMP7 AG基因型是肺癌易感因子,約是AA基因型的1.75倍(OR=1.75,95%CI=1.45-2.69)。MMP7基因SNP與肺癌臨床病理學(xué)參數(shù)無相關(guān)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.
【學(xué)位授予單位】：湖南工業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R734.2

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