云南省煤煙污染高暴露地區(qū)中肺癌相關(guān)基因的DNA甲基化研究
發(fā)布時間：2018-10-30 07:09
【摘要】：背景與目的:目前,肺癌是全世界常見且發(fā)病率和死亡率均居于首位的惡性腫瘤疾病,隨著我國城市化和工業(yè)化的進程不斷加快,人口的持續(xù)增長和人口結(jié)構(gòu)趨向老齡化,加上周邊環(huán)境污染日益嚴峻以及人們不良生活方式的養(yǎng)成(主要是吸煙)等各種因素聯(lián)合的影響下,中國的肺癌發(fā)病率和死亡率仍然保持快速上升趨勢。研究報道證實吸煙是誘導(dǎo)肺癌發(fā)生的主要危險因素,而作為全世界知名肺癌高發(fā)地區(qū)的中國云南省曲靖地區(qū),其肺癌高發(fā)主要是因為長期生活在煙煤暴露環(huán)境。本論文想通過表觀遺傳學(xué)機制手段(如DNA甲基化)研究相關(guān)肺癌基因在云南省煤煙污染高暴露地區(qū)及對照地區(qū)中的的DNA甲基化變化,分析煙煤暴露因素及吸煙因素對肺癌的影響,來闡釋云南等地肺癌高發(fā)的機制,同時希望能為DNA甲基化異常運用到肺癌的早期診斷和環(huán)境致癌物在肺癌中的作用研究提供理論支持,并為后續(xù)研究云南本地環(huán)境暴露對肺癌發(fā)生發(fā)展機制研究提供基礎(chǔ)。方法:選取文獻報道中與吸煙顯著性關(guān)聯(lián)的基因RUNX3,同時挑選APC及PCDH20基因作為對照,并運用實時熒光定量甲基化特異性基因PCR擴增技術(shù)(即qMSP)在67例肺癌患者樣本、23例非肺癌患者以及12例正常人患者全血樣本中檢測其DNA甲基化水平。結(jié)果:APC、PCDH20、RUNX3三個基因均與肺癌發(fā)生發(fā)展相關(guān),且肺癌患者中RUNX3基因在曲靖高煙煤暴露地區(qū)的肺癌患者中具有顯著性差異(P=0.001)。本文研究發(fā)現(xiàn):在云南曲靖地區(qū)中,RUNX3基因啟動子區(qū)的DNA甲基化與煙煤燃燒年限及吸煙都有顯著性關(guān)聯(lián)(P0.05),但在進一步研究中并未發(fā)現(xiàn)吸煙與煙煤燃燒之間存在共同聯(lián)系。在肺癌患者中,RUNX3基因在鱗癌與腺癌分型中的DNA甲基化變化有顯著性差異,且在腺癌類型中的甲基化率是要明顯高于鱗癌類型;此外,研究分析發(fā)現(xiàn)RUNX3基因的DNA甲基化與云南當?shù)匦詣e、地區(qū)分布有關(guān)聯(lián),在男性中RUNX3基因的DNA甲基化在曲靖與昭通地區(qū)、曲靖與昆明地區(qū)有顯著性差異;而女性在不同地區(qū)之間均有顯著性差異。主要結(jié)論:RUNX3基因可作為研究云南省煤煙污染高暴露地區(qū)中肺癌相關(guān)基因的異常DNA甲基化的潛在標志物之一。
[Abstract]:Background & objective: at present, lung cancer is a common malignant disease with the highest morbidity and mortality in the world. With the accelerating process of urbanization and industrialization in China, the population continues to grow and the population structure tends to be aging. Combined with the increasingly severe environmental pollution and the combination of various factors, such as the formation of people's unhealthy lifestyle (mainly smoking), the morbidity and mortality of lung cancer in China have maintained a rapid upward trend. It is confirmed that smoking is the main risk factor of lung cancer, and the high incidence of lung cancer in Qujing area of Yunnan Province is mainly due to long-term exposure to bituminous coal. The purpose of this study was to study the changes of DNA methylation of lung cancer genes in high exposure areas and control areas of Yunnan province by means of epigenetic mechanisms such as DNA methylation. In order to explain the mechanism of high incidence of lung cancer in Yunnan and other places, the factors of exposure to bituminous coal and the influence of smoking factors on lung cancer were analyzed. It also hopes to provide theoretical support for the early diagnosis of lung cancer with abnormal DNA methylation and the role of environmental carcinogens in lung cancer, and provide a basis for further study on the mechanism of occurrence and development of lung cancer caused by local environmental exposure in Yunnan Province. Methods: APC and PCDH20 genes were selected from RUNX3, a gene associated with smoking, and real-time quantitative methylation specific gene PCR amplification (qMSP) was used in 67 patients with lung cancer. DNA methylation levels were detected in blood samples from 23 patients with non-lung cancer and 12 normal controls. Results: all the three APC,PCDH20,RUNX3 genes were related to the occurrence and development of lung cancer, and the RUNX3 gene was significantly different in the lung cancer patients in Qujing high bituminous coal exposure area (P0. 001). It was found that DNA methylation in the promoter region of RUNX3 gene was significantly associated with the burning years of bituminous coal and smoking in Qujing area of Yunnan Province (P0.05). However, no common link between smoking and bituminous coal combustion was found in further studies. In patients with lung cancer, there was significant difference in DNA methylation between squamous cell carcinoma and adenocarcinoma, and the methylation rate in adenocarcinoma was significantly higher than that in squamous cell carcinoma. In addition, the DNA methylation of RUNX3 gene was associated with the local sex and regional distribution of Yunnan, and the DNA methylation of RUNX3 gene was significantly different between Qujing and Zhaotong, Qujing and Kunming. There were significant differences among women in different regions. Conclusion: RUNX3 gene can be used as a potential marker for the study of abnormal DNA methylation of lung cancer related genes in high exposure areas of coal smoke pollution in Yunnan Province.
【學(xué)位授予單位】：昆明理工大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R734.2
[Abstract]:Background & objective: at present, lung cancer is a common malignant disease with the highest morbidity and mortality in the world. With the accelerating process of urbanization and industrialization in China, the population continues to grow and the population structure tends to be aging. Combined with the increasingly severe environmental pollution and the combination of various factors, such as the formation of people's unhealthy lifestyle (mainly smoking), the morbidity and mortality of lung cancer in China have maintained a rapid upward trend. It is confirmed that smoking is the main risk factor of lung cancer, and the high incidence of lung cancer in Qujing area of Yunnan Province is mainly due to long-term exposure to bituminous coal. The purpose of this study was to study the changes of DNA methylation of lung cancer genes in high exposure areas and control areas of Yunnan province by means of epigenetic mechanisms such as DNA methylation. In order to explain the mechanism of high incidence of lung cancer in Yunnan and other places, the factors of exposure to bituminous coal and the influence of smoking factors on lung cancer were analyzed. It also hopes to provide theoretical support for the early diagnosis of lung cancer with abnormal DNA methylation and the role of environmental carcinogens in lung cancer, and provide a basis for further study on the mechanism of occurrence and development of lung cancer caused by local environmental exposure in Yunnan Province. Methods: APC and PCDH20 genes were selected from RUNX3, a gene associated with smoking, and real-time quantitative methylation specific gene PCR amplification (qMSP) was used in 67 patients with lung cancer. DNA methylation levels were detected in blood samples from 23 patients with non-lung cancer and 12 normal controls. Results: all the three APC,PCDH20,RUNX3 genes were related to the occurrence and development of lung cancer, and the RUNX3 gene was significantly different in the lung cancer patients in Qujing high bituminous coal exposure area (P0. 001). It was found that DNA methylation in the promoter region of RUNX3 gene was significantly associated with the burning years of bituminous coal and smoking in Qujing area of Yunnan Province (P0.05). However, no common link between smoking and bituminous coal combustion was found in further studies. In patients with lung cancer, there was significant difference in DNA methylation between squamous cell carcinoma and adenocarcinoma, and the methylation rate in adenocarcinoma was significantly higher than that in squamous cell carcinoma. In addition, the DNA methylation of RUNX3 gene was associated with the local sex and regional distribution of Yunnan, and the DNA methylation of RUNX3 gene was significantly different between Qujing and Zhaotong, Qujing and Kunming. There were significant differences among women in different regions. Conclusion: RUNX3 gene can be used as a potential marker for the study of abnormal DNA methylation of lung cancer related genes in high exposure areas of coal smoke pollution in Yunnan Province.
【學(xué)位授予單位】：昆明理工大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R734.2
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