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病原因子致原发性肝癌的流行病学及相关信号通路研究
The Study of Epidemiology and Signal Pathway in Etiology of Hepatocellular Carcinoma
【作者】 居颖;
【导师】 陈冬峨;
【作者基本信息】 武汉大学 , 流行病与卫生统计学, 2005, 硕士
【摘要】 目的:(1)利用肝癌历史登记资料和查阅数据的方式,简要回顾调查湖北省城乡居民男性和女性肝癌死亡率变化趋势,为该地区男性和女性肝癌的流行病学研究提供线索。(2)采用临床流行病学方法中的抽样调查方式,进一步探讨武汉地区居民原发性肝细胞癌(HCC)的危险因素及其变化,以期了解病因模式、为采取有效预防措施提供科学依据。(3)采用分子流行病学相应指标研究不同癌基因、抑癌基因以及信号通路中生长因子及其受体对原发性肝癌发生、发展、转归的风险度,为原发性肝癌研究寻找基因水平的理论依据。 材料与方法:(1) 回顾湖北省90年代的相关原发性肝癌的登记资料,加以汇总分析讨论,人口资料来自湖北年鉴(湖北省统计局编),人口采用世界标准人口和全国人口普查年龄构成进行标化处理后,进行比较,观察趋势分布。(2)选取2000年1月1日—2003年7月31日期间在武汉大学中南医院、武汉陆军总医院就诊的HCC患者,共计313例。纳入病例排除其他部位肿瘤的肝脏转移患者。诊断依据:B超[或CT]有占位性病变以及实验室检查指标:AFP、ALT、AST等,结合临床观察,部分病例还经肝细胞活检病理证实。选取同时期、同医院就诊的非肝癌的消化道肿瘤患者作为对照人群。对照的选择首先根据成组设计原则,按单纯随机抽样方法在对照人群中随机抽取313例非肝癌患者,组成对照组。 调查内容主要包括:一般人口学特征(年龄、性别、职业、教育程度、婚姻状况等)、乙型肝炎病史、吸烟(是否吸烟、吸烟时间、数量等)、饮酒(是否饮酒、饮酒时间、数量等)、饮茶史(是否饮茶及饮茶的种类和频率)、肿瘤家族史、膳食情况(包括平时的饮食习惯及食物摄入量等)等共70余项指标。实验室检测包括血型测定,采用ELISA法检测血清中HBsAg、HBs-Ab、HBeAg、HBe-Ab、HBcAg、HBc-Ab、抗-HCV。 本研究应用SPSS和SAS统计软件包,对样本首先进行单因素分析,然后将单因素分析结果中显著性水平小于0.10的因素,通过逐步回归分析(stepwise),
【Abstract】 Objective(l)We collected the mortality data of hepatocellular carcinoma in 1990-1999in Hubei province.Incidence and mortality data in 1990-1999 from hepatocellular carcinoma registry records and many relative documents, in order to provide some cues for epidemiological research..(2)Exploring the major risk factors and etiologic model of hepatocellular carcinoma by clinical epidemiological study,so as to acquire the scientific basis for preventive measures in further.(3)Adopt investigating the risk degree of different oncogenes and anti-oncogenes and growth factors with its receptors in signal pathway about hepatocellular carcinoma(HCC)’s occurrence 、progress , in order to look for the according to theories at the genetic level for the basic study of hepatocellular carcinoma(HCC).Materials and Method(l)Look back the registered data of the related HCC,of the liver of the 90’s of Wuhan City, take in to gather the analytical discussion, the population data comes from the Aannals which be published by the statistics bureau of Hubei province , standard population in world and national census ages of the population are used to be adjusted standard.Then we can carry on the result of the comparison and observe the trends to distribution.(2)Alimentary tract tumors were formed the cohort set of this study, all were hospitalized in Wuhan university Zhongnan Hospital or Wuhan Army Hospital in 1st January, 2000 to 31st July, 2003. Eliminating secondary liver cancer, 313 hepatocellular carcinomas were formed the case group of this study. Diagnosis basis is B ultrasonic wave or CT and index of laboratory, for example, AFP, ALT, AST and so on, combining with clinical symptom, some of cases were done pathological Biopsy. Two methodswere used to select controls in this study. Firstly, for each case, one other alimentary tract tumors was randomly selected from the cohort set as control, resulting a final control group of 313 individualsThe study was based on the questionnaire by graduate student Public Health School Wuhan University. The study content composed of general characteristics, personal habits and history of viral hepatitis, family history of tumor and the habit of dietary, including sex, age, profession, education, dietary habit, alcohol consumption, cigarette smoking and drinking tea and so on. The index of laboratory include HBsAg, HBsAb, HbeAg, HBeAb, HbcAg, HBcAb and HCV-Ab by Enzyme-linked immunoadsordent assay (ELISA).SPSS and SAS were used to analyze data in this study. Univariate analysis was the first analyzing step for sample Then, variables showing associations with the risk of Hepatocellular carcinoma at P<0.10 level were further tested in stepwise non-conditional and conditional Logistic regression models for the sample, respectively. The final model consisted of those variables showing a significant level at PO.05. OR value and its 95% CI were calculated for these factors.(3)Search documents by computer, handiwork and retrospective and undertake quality assessment to eliminate articles which is repeatly reported, ropy , not integrated or little information according to Lichtenstein criterion.Result(1) The cancer of the liver is one of the common malignant tumors in our country . The malignant degree of the disease is high,it develop quickly, be cured thedifficultly, as the third importantant factor in deadly tumor disease of Hubei province, respectively 20.21% in male,and 12.59% in female, a difference of men and women shows that the patients in male are more than in female.(2) From the sample , age was closely associated with HCC, the result showed that the incidence of HCC increased as age increased, it reached the max at the age of 40 to 50 years old, then drop down as age increased. The result showed that the averagediagnosed age of HCC was 50.68±12.807, significantly younger than that of controls, which was 57.54±13.652 years old (PO.001).In the univariate analysis of sample 1, compared with female, the OR value of male for HCC was 4.9968. In different profession and education, it suggested that fatalness for HCC with people in high-tech was high, its OR values were 1.163, 1.273, respectively. After transforming the profession and blood type into dunny variable, it was suggested that peasan, technology personnel and A blood type were correlation with HCC, which OR values were 1.613, 0.520,1.867, respectively.The result of multivariate analysis showed that the main risk factors were sex, the history of Hepatitis B, cigarette smoking, age at start to smoking, seropositives of HBcAb in the sample, only the history of Hepatitis B and the amount of smoking per day entered the Logistic regression model, whose OR value were 15.294,1.252.The analysis of Synergism showed that risk of sex, cigarette smoking, age at start to smoking, seropositives of HBcAb were increased together with the history of Hepatitis B, compared with the risk of each single factor. The results showed that the major risk factors can play the interaction on the HCC.(3)The positive expression of oncogene and anti-oncogene and growth factors with its receptors in signal pathway were at hepatocellular carcinoma and gastric carcinoma. The positive rate of P53, P2iras , be 1-2, C-erbB-2, C-myc were significant difference between hepatocellular carcinoma and besides it.Conclusion(l)The incidence and mortality the cancer of the liver in HUBEI From the instevagation we shouled attach importance to these aspect workings, Be care of the sex difference, strengthenning the disease prevention in early days.(2)Factors founded in this study, which were closely associated with HCC, were sex, cigarette smoking, the history of Hepatitis B in sample 1, and cigarette smoking, the history of Hepatitis B in sample 2. Moreover, factors such as alcohol consumption, seropositives of HBsAg, HBeAg, HBeAb, HBcAg, HBcAb although showed asignificant OR level in univariate statistic analysis, they did not enter the final Logistic regression models.(3)epidemiological study on laboratory data on Web showed that oncogene and anti-oncogene and growth factors with its receptors in signal pathway play a promotive role in the tumorigenesis and development of carcinoma, at present it was indetermination to diagnose hepatocellular carcinoma by gene.
【Key words】 hepatocellular carcinoma; risk factor; growth factor; Epidemiological Survey; oncogene; signal pathway;
- 【网络出版投稿人】 武汉大学 【网络出版年期】2006年 05期
- 【分类号】R735.7
- 【下载频次】189