【作者】 陈波；

【导师】 秦江梅；

【作者基本信息】 石河子大学 ， 流行病与卫生统计学， 2008， 硕士

【摘要】 目的:1.探讨CYP2E1基因遗传多态性与新疆哈萨克族(以下简称哈族)食管癌发病的相关性;2.探讨CYP2E1基因代谢相关因素在新疆哈族食管癌发病中的作用;3.探讨CYP2E1基因遗传多态性及其代谢相关因素的交互作用与新疆哈族食管癌发生的关联。方法:1.采用以医院为基础的1∶2配对的病例对照研究,病例来自于新疆北部六所医院2005年3月至2007年4月经内窥镜及病理诊断确诊为食管癌的哈族新发病例,共120例;对照选择与病例在年龄、性别、民族和居住地相匹配的同期入院的非肿瘤患者及正常人群,共240例,对所有研究对象进行血液标本的采集和生活行为因素的流行病学调查;2.采用聚合酶链反应(PCR)技术检测120例哈族食管癌患者和240例哈族对照人群血清中的CYP2E1基因RsaI位点的基因型分布;3.统计处理利用SPSS13.0软件包,采用χ2检验、条件Logistic回归分析方法,计算相对危险度(OR)及其95%可信区间,检验基因型分布是否符合Hardy-Weinberg平衡定律。结果:1. CYP2E1基因与哈族食管癌易感性的研究结果显示:在对照组中,CYP2E1三种基因型C1/C1、C1/C2、C2/C2频率分别为53.3%、37.5%、9.2%,而在食管癌组中分别为78.3%、19.2%、2.5% ,经统计学检验,差异有统计学意义(χ2=21.794,df=2,P=0.000);携带C1/C1基因型发生食管癌的危险性是携带C1/C2或C2/C2基因型的3.07倍(95%CI:1.87～5.03);等位基因C1携带者发生食管癌的危险性为C2的2.818倍(95%CI:1.821～4.360)。2.分析与CYP2E1相关的危险因素:CYP2E1C1/C1基因型、饮水类型、吸烟、饮酒和家族史等8个因素是哈族食管癌发生的危险因素,使用冰箱是其保护因素。3.将单因素分析有意义的变量进行多因素条件Logistic回归分析,结果显示:饮水类型、吸烟量、饮酒、食用陈粮、腌菜、使用冰箱和CYP2E1C1/C1基因型7个因素进入多因素模型。4.CYP2E1基因与其代谢相关环境因素交互作用分析显示:CYP2E1C1/C1基因型与饮水类型、吸烟量、饮酒、食用陈粮和腌菜、使用冰箱均存在交互作用。结论:1.CYP2E1C1/C1基因型和不良的饮食生活习惯是哈族食管癌发生的危险因素。2.通过基因-环境因素的交互作用分析提示:控制哈族居民的饮用水污染和饮食卫生,戒烟、戒酒可降低携带CYP2E1RsaI位点C1/C1基因型者发生食管癌的危险性。更多还原

【Abstract】 Objective:1. To the association between CYP2E1 gene polymorphrisms and esophageal cancer(EC) in Xinjiang Kazakh;2. To study CYP4502E1 gene polymorphrism and with risk to develop of Esophageal Cancer(EC) in Kazakh.3. To explore the gene-environment interaction between the CYP2E1 gene polymorphrism and its related metabolic factors with ES in Kazakh.Method:1. Using 1:2 matched case-control study, we have identified 120 esophageal cancer patients with endoscopy and pathology diagnosis from hospital in north of Xinjiang during the periods from March 2005 to June 2007.A total of 240 controls without history of malignant tumor or digestive system diseases were selected during the same period as cases and matched to each case by gender, age, nationality and inhabited areas All the studies conducted on the blood samples and the life behavioral factors epidemiological investigation;2. CYP2E1 genotypes were identified by PCR amplification followed by digestion with RsaI;3. All the calculations and statistics were performed with the computer program, SPSS Version 13.0. Statistical analysises adoptχ2 test, conditional logistic regression to calculate the values ofχ2, odds ratios and 95% confidence intervals for possible risk/protective factors. Check the accordance with Hardy-Weinberg equilibrium in the group.Result:1. The frequencies of C1/C1、C1/C2 and C2/C2 were 53.3%、37.5%and 9.2% in Kazakh’s controls and 78.3%、19.2%、2.5% in Kazakh’s individuals with EC, The genotype frequencies of EC group is different from controls group (χ2=21.794,df=2,P=0.000). The individuals with C1/C1genotype had a 3.07-fold (95%CI: 1.87～5.03) increased risk of developing EC, The allele C1 of CYP2E1 had a 2.818-fold (95% CI : 1.821～4.360) increased risk of developing EC compared with those who had allele C2.2. Analysis the risk factors related CYP2E1, showed: CYP2E1C1/C1 genotypes,not sanitation of drinking water, excessive smoking,drinking wine ,family history of EC ten factors were risk factors of EC, the use of refrigerators is the protect factor of EC.The use of refrigerators was the protect factor of EC.3. Multivariate conditional Logistic regression analysis showed: not sanitation of drinking water, excessive smoking,drinking wine, eating old grain and pickles, using the refrigerator and CYP2E1C1/C1were important risk factors of EC.4. The interaction shows:Between the CYP2E1C1/C1 genotype and not sanitation of drinking water, excessive smoking,drinking wine, eating old grain and pickles, using the refrigerator have the correlation.Conclusion:1. CYP2E1C1/C1 genotype and diet habits were risk factors of EC in Kazakh of Xinjiang.2.Interaction between gene and entironment showed that:not sanitation of drinking water, excessive smoking,drinking wine, eating old grain and pickles and not using the refrigerator , may reduce fatalness with CYP2E1C1/C1genotype crowds to have esophagus cancer’s risk in Kazakh Xinjiang.更多还原