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哈萨克族食管癌与易感基因多态关系及免疫相关因素研究

Study on Genetic Polymorphisms and Related Factors of Immunofunction in Kazakh’s Esophageal Cancer

【作者】 张力为

【导师】 吴明拜;

【作者基本信息】 新疆医科大学 , 心血管内科, 2006, 博士

【摘要】 目的:新疆是中国食管癌高发区之一,13个世居民族中哈萨克族人群(人口约200万),具有明显的地区性和家族聚集性,其在食管癌民族发病率中最高,调整死亡率达68.88/10万,为早期发现该民族食管癌患者以及降低其发病率与死亡率,本研究从食管癌发病的基因分子学角度及免疫的相关因素展开研究,探索其防治的新途径。该研究以新疆哈萨克族食管癌防治研究已有的基础为起点,从哈萨克族常用的食物受亚硝胺、多环芳烃等化学致癌物的长期污染入手,同时结合其生活习惯(吸烟、饮酒)等,探索叶酸代谢酶、致癌物代谢酶基因遗传多态性对环境致癌物的致癌效应所起的作用;利用先进的流式细胞技术(FCM)研究和探索该民族食管癌患者机体免疫状态的变化,检测血清中相应的细胞因子水平的变化,分析T淋巴细胞亚群的免疫活动,进一步了解该民族食管癌的发病机制。通过以上的研究,可为新疆哈萨克族食管癌的早期诊断、早期治疗提供科学指导依据,同时也为其在手术治疗后免疫调控方面提供科学的理论依据。 方法:①收集经组织病理学确诊的哈萨克族食管鳞癌新发病例88例外周血液标本提取DNA;72例健康哈萨克族人群作为对照,同时调查每个研究对象的吸烟、饮酒情况。以聚合酶链反应方法进行MTHFR、CYP2C19、GSTT1基因扩增:用PCR-限制性片段长度多态性技术检测研究对象的MTHFR 1298A→C、CYP 2C19ml、CYP

【Abstract】 Objective: Esophageal cancer(EC) is a common disease in several areas of central Asia, including Xinjiang Uigur Autonmous Region, north of China. The incidence of Kazakh’s EC has been considered as the highest among population in Xinjiang, and its aged-adjusted mortality rate up to 68.88/100, 000 reported by epidemiological study. The Kazakh population was estimated to be as 13 million around the world including 10million Kazakh distributed in Kazakhstan and 2 million in Xinjiang, north of China. The population in the current study was a Kazakh isolated community, which located at the northwest of Xinjiang. The genetic homogeneity and geography stability of the population, along with shared exposure to common environmental variables, may provide an excellent opportunity for the study on genetic influence for EC. These cancers are mostly squamous cell carcinoma (SCC). The series studies have suggested that a number of risk factors be involved in the carcinogenesis for Kazakh’s ESCC, including deficiencies in vitamins and minerals, consumption of pickled foods and environmental exposure to specific nitrosamines, genetic susceptibility, etc.The high incidence in special areas indicated the importance of environment factors in esophageal etio-carcinogenesis. Only a small part of individuals in the high-risk area developed into EC although all the residents in that area may share very similar environment-related factors, such as the polymorphism of phase- I (CYP2C19)and phase-II enzymes (GSTT1), methylenetetrahydrofolate (MTHFR) may play an important

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