Risk Study On Risk Factor And Apoptosis Related Gene Of Primary Hepatic Carcinoma

Objective(1) Comprehensively analyzing and evaluating the relative risk factors of Primary Hepatic Carcinoma so as to provide a scientific basis for effective measures preventing and controlling the disease's happening and development.(2) Exploring the major risk factors of Primary Hepatic Carcinoma by clinical epidemiological study and understanding the etiologic model of PHC in Wuhan, in order to provide a scientific basis for local preventive measures.(3) Exploring the effects and significane of the expression of apoptosis gene "Fas sFas Bcl-2 and Bax" during the liver cancer's happening and development and its relationship with carcinoma biological behavior so as to provide a theoretical basis on the gene level in search for Primary Hepatic Carcinoma.Materials and Methods(1) Collecting published literatures on case-control studies related to risk factors about Primary Hepatic Carcinoma during the past ten years from 1994 to 2004 in China. The homogeneity tests were used to analyze literature up to inclusion criterion. Fixed effect model or random effect model of Meta-analysis were selected to calculate pooled OR and 95% OR confidence intervals.(2) Selecting 328 patients with PHC as the case group and 340 patients with the enteron tumor other than PHC from the same period and hospital as the control group by cluster sampling method, all of whom were treated in ZhongNan Hospital of Wuhan University and Wuhan General Hospital of Guangzhou Command of PLA from Jan, 2000 to July, 2003. The seven serum markers — HbsAg, HBsAb, HBeAg, HBeAb, HBcAg, HBcAb and anti-HCV — were measured by means of Enzyme-Linked -Immonosorbent Assay (ELISA) on all the patient. All the data was input into the Microsoft Access Database, and analyzed with the statistical software of SAS8.1 andSPSS 11.5 (Windows edition). The main statistical methods were non-conditional Logistic Regression, chi-square test and Wilcoxon test.(3) Adopting the statistical method of meta analysis to collect and analyze the related literatures about relative apoptosis gene and Primary Hepatic Carcinoma during the early ten years from 1994-2004, so as to reveal the laboratory studies' status in quo about the apoptosis gene of Primary Hepatic Carcinoma.Results(1) Thirty-nine literatures referred to case-control studies on Primary Hepatic Carcinoma were selected. The results indicated that the OR and its 95%CI of the related risk factors of Primary Hepatic Carcinoma in China were the total infection of HBV 23.07 (13.62-39.10), HBsAg 13.11 (11.55-14.89), HBeAb 12.07 (4.73-30.81), HBcAb 10.23 (5.32-19.64), the history of Hepatitis B 8.54 (4.82-15.11), chronic hepatitis 8.06 (5.50-11.83), HBeAg 7.03 (4.57-10.81), the history of liver carcinoma 4.60 (3.05-6.95), Hepatitis C 3.56 (2.69-4.71), psychic stimulation 2.86 (1.77-4.63), ect; on the other side, the other two variable—HBsAb and eating fruit and vegetable had protective function to the development of Primary Hepatic carcinoma, whose OR (OR95% CI) was 0.27 (0.18-0.41) and 0.70 (0.49-0.99) respectively.(2) The positive rate of HBsAg in patients with PHC (63.11%) was significantly higher than that in control group with non-PHC (11.47%), In the cases of PHC, the positive rate of the combination of HBsAg, HBeAb and HBcAb was 37.2%, which was significantly higher than that of the combination of HBsAg, HBeAg and HBcAb (6.4%). According to the results of liver function testing, there was no significant difference between the group with the combination of HBsAg(+), HBeAb(+), HBcAb(+) and the group with the combination of HBsAg(+), HBeAg(+) and HBcAb(+) (P>0.05). Hepatic injury in cases of PHC was significantly higher than that in control group of non-PHC (PO.01). One-way analysis of Logistic regression showed that thirteen variables - sex, the history of Hepatolellular Carcinoma, HCV, smoking, drinking, HBsAg, HBsAb, HBeAg, HBeAb, HBeAg, HBcAb, duration of smoking, duration of drinking - wereassociated with PHC's happening. All the variables with statistical significance were entered into the multiple-factor analysis of non- conditional Logistic regression model. The result showed that five risk factors that entered into the model were the history of Hepatolellular Carcinoma 2.594 (1.951-7.077), HCV 4.611 (1.601-13.279), drinking 1.622 (1.010-2.605) and HBsAg 8.441 (5.410-13.171).(3) Twenty-one literatures referred to apoptosis related gene studies on the Primary Primary Hepatic Carcinoma were selected. There were different expressions of apopotosis related gene about Fas sFas Bcl-2 and Bax among cancerous tissues, paracarcinomatous tissues and normal control group tissues. ?The positive expression ratio of Fas in paracarcinomatous tissues was 33.47 percent higher than that in Primary Hepatic Carcinoma on average. The positive expression ratio of Bcl-2 was not significantly different between in Primary Hepatic Carcinoma and in paracarcinomatous tissues. The positive expression ratio of Bax in paracarcinomatous tissues was 39.38 percent higher than that in Primary Hepatic Carcinoma on average. ?The level of serum soluble Fas increased 1.6331 in PHC group as compared with normal control group. ?There was a strongly significant relationship between apoptosis gene including Fas and Bcl-2 and Primary Hepatic Carcinoma's happening. The value of OR (95% OR CI) was 5.9816 (1.8779-19.0536), 4.7999 (2.1344-10.7931) respectively. Bax had protective effect to the PHC's occurrence, the value of OR was 0.2780 (0.1471-0.5255) . ?The positive expression ratio of Bax was all higher than that of Bcl-2 in Primary Hepatic Carcinoma, paracarcinomatous tissues and normal control group tissues, whose reduced value were 9.13%, 44.8% and 57.58% among these three tissues respectively. Conclusion(1) The main risk factors on Primary Hepatic Carcinoma in turn were the total infection of HBV, HBsAg, HBeAb, HBcAb, the history of liver carcinoma, chronic hepatitis and so on. Comprehensive measures against these related risk factors should be taken in order to prevent and control the occurrence of Primary Hepatic Carcinoma. Inconclusion, Primary Hepatic Carcinoma is the interactional result from multi-factors, multi-ways and multi-stages. It is high time to implement primary prevention according to the causes of Primary Hepatic Carcinoma at present.(2) Exploring on risk factors of PHC by the method of clinical epidemiology showed that the chronic hepatitis B virus infection is playing extremely important role in PHC's etiology. The human group who were positive with HBsAg, HBeAb and . HBcAb is the PHC's high-risk group.(3) Primary Hepatic Carcinoma's happening and development may be related to the constrained expression of the cellular apoptosis gene, and be controlled by Apoptosis Related Gene. The effect of stimulative apoptosis gene of Fas is constrained in the Primary Hepatic Carcinoma tissues. The change of ratio of Bcl-2/Bax influences the apoptosis status of hepatocyte, All the above factors play important roles in the happening of Primary Hepatic Carcinoma.