云南省煤烟污染高暴露地区中肺癌相关基因的DNA甲基化研究
发布时间：2018-10-30 07:09
【摘要】：背景与目的:目前,肺癌是全世界常见且发病率和死亡率均居于首位的恶性肿瘤疾病,随着我国城市化和工业化的进程不断加快,人口的持续增长和人口结构趋向老龄化,加上周边环境污染日益严峻以及人们不良生活方式的养成(主要是吸烟)等各种因素联合的影响下,中国的肺癌发病率和死亡率仍然保持快速上升趋势。研究报道证实吸烟是诱导肺癌发生的主要危险因素,而作为全世界知名肺癌高发地区的中国云南省曲靖地区,其肺癌高发主要是因为长期生活在烟煤暴露环境。本论文想通过表观遗传学机制手段(如DNA甲基化)研究相关肺癌基因在云南省煤烟污染高暴露地区及对照地区中的的DNA甲基化变化,分析烟煤暴露因素及吸烟因素对肺癌的影响,来阐释云南等地肺癌高发的机制,同时希望能为DNA甲基化异常运用到肺癌的早期诊断和环境致癌物在肺癌中的作用研究提供理论支持,并为后续研究云南本地环境暴露对肺癌发生发展机制研究提供基础。方法:选取文献报道中与吸烟显著性关联的基因RUNX3,同时挑选APC及PCDH20基因作为对照,并运用实时荧光定量甲基化特异性基因PCR扩增技术(即qMSP)在67例肺癌患者样本、23例非肺癌患者以及12例正常人患者全血样本中检测其DNA甲基化水平。结果:APC、PCDH20、RUNX3三个基因均与肺癌发生发展相关,且肺癌患者中RUNX3基因在曲靖高烟煤暴露地区的肺癌患者中具有显著性差异(P=0.001)。本文研究发现:在云南曲靖地区中,RUNX3基因启动子区的DNA甲基化与烟煤燃烧年限及吸烟都有显著性关联(P0.05),但在进一步研究中并未发现吸烟与烟煤燃烧之间存在共同联系。在肺癌患者中,RUNX3基因在鳞癌与腺癌分型中的DNA甲基化变化有显著性差异,且在腺癌类型中的甲基化率是要明显高于鳞癌类型;此外,研究分析发现RUNX3基因的DNA甲基化与云南当地性别、地区分布有关联,在男性中RUNX3基因的DNA甲基化在曲靖与昭通地区、曲靖与昆明地区有显著性差异;而女性在不同地区之间均有显著性差异。主要结论:RUNX3基因可作为研究云南省煤烟污染高暴露地区中肺癌相关基因的异常DNA甲基化的潜在标志物之一。
[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.
【学位授予单位】：昆明理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：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.
【学位授予单位】：昆明理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2
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