乙型肝炎病毒基本核心启动子和前C区突变与肝硬化肝细胞癌和非肝硬化肝细胞癌发生的关系  

The relationship between the hepatitis B virus base core and precore/core promoter mutations and thedevelopment of cirrhotic hepatocellular carcinoma and noncirrhotic hepatocellular carcinoma

作　　者：徐尧江 宋伟泉 张要栋 陈永刚 王凯憎 

机构地区：[1]浙江省上虞市人民医院感染疾病科,312300

出　　处：《中华传染病杂志》2012年第12期721-726,共6页Chinese Journal of Infectious Diseases

摘　　要：目的研究慢性HBV感染者抗病毒治疗前HBV基本核心启动子（BCP）和前C区突变与肝细胞癌发生的关系。方法收集2003年1月至2010年12月浙江省上虞市人民医院感染疾病科门诊和住院收治的慢性HBV感染患者，其中慢性乙型肝炎166例（对照），肝硬化肝细胞癌患者158例和非肝硬化肝细胞癌患者57例，采用PCR扩增后直接测序法检测HBVBCP和前C区突变，同时确定基因型。数据采用X2检验及Logistic回归分析。结果患者以HBV基因B型为主，其中慢性乙型肝炎有124例，肝硬化肝细胞癌有126例，非肝硬化肝细胞癌有50例。以慢性乙型肝炎患者作为对照组，在单变量分析中BCPV1753突变（X2=7．927，P=0．005）、BCPT1762／A1764双突变（X2=12．796，P〈0．01）、前C区A1896突变（X2=6．890，P=0．009）和前c区A1899突变（X2=11．850，P=0．001）与肝硬化肝细胞癌的发生有关；前C区A1896突变（X2=27．310，P〈0．01）和前c区A1899突变（X2=7．575，P=0．006）与非肝硬化肝细胞癌的发生有关。多因素Logistic回归分析发现，在HBeAg阳性患者中，BCPT1762／A1764双突变（wald=6．180，P=0．016，OR=8．883）和前C区A1899突变（wald=10．279，P=0．001，OR=7．475）是肝硬化肝细胞癌发生的危险因素；前C区A1896突变（wald=4．324，P=0．038，OR=4．439）和前c区A1899突变（wald=4．850，P=0．028，OR=6．010）是非肝硬化肝细胞癌发生的危险因素。在HBeAg阴性患者中，仅前C区A1896突变（wald=15．448，P〈O．01，OR=12．128）是非肝硬化肝细胞癌发生的危险因素。结论BCPT1762／A1764双突变与HBeAg阳性患者的肝硬化肝细胞癌发生有关，前C区A1896突变与HBeAg阳性和阴性患者的非肝硬化肝细胞癌发生有关，前C区A1899突变与HBeAg阳性患者的肝硬化肝细胞癌和非肝硬化肝细胞癌发生有关。Objective To investigate the mutations of basal core promoter （BCP） and precore （PreC） region of hepatitis B virus （HBV） and the association with the development oI hepatocellutar carcinoma in patients with chronic HBV infection. Methods Totally 381 untreated HBV patients were recruited from the Department of Infectious Diseases, People% Hospital of Shangyu from Jan 2003 to Dec 2010, which included patients with chronic hepatitis B （CHB, n= 166）, cirrhotic hepatocellular carcinoma （cirrhotic-HCC, n = 158） and noncirrhotic hepatocellular carcinoma （noncirrhotic-HCC,n= 57）. The mutations in HBV BCP and PreC and the genotypes of HBV were determined by polymerase chain reaction （PCR） and direct sequencing. Data were analyzed by chi square test and Logistic regression. Results The HBV genotype of most cases was genotype B （CHB, n= 124 cirrhotic-HCC, n= 126 noncirrhotic-HCC, n= 50）. In univariant analysis, BCP V1753 （2 = 7. 927, P=0. 005）, BCP T1762/A1764 （）C =12. 796, P〈0.01）, PreC A1896 （X2=6. 890, P=0. 009） and PreC A1899 X2 = 11. 850, P = 0. 001） mutations were more frequently detected in cirrhotic-HCC patients than those in CHB patients. PreC A1896 X2 =27. 310, P〈0.01） and A1899 （X2 =7. 575, P= 0. 006） mutations were highly detected in noncirrhotic-HCC patients than those in CHB patients. Multivariate Logistic regression analysis revealed that in HBeAg positive patients, BCP T1762/A1764 （wald=6. 180, P=0. 016, OR=8. 883） and PreC A1899 （wald=10.279, P=0. 001, OR=7. 475） mutations were independently associated with the development of cirrhotie-HCC PreC A1896 （wald=4.324, P=0.038, OR=4. 439） and PreC A1899 （wald=4. 850, P=0. 028, OR=6. 010） mutations were independently associated with the development of noncirrhotic-HCC. While in HBeAg negative patients, PreC A1896 mutation （wald= 15. 448, P〈0.01, OR= 12. 128） was independently associated with the development of noncirrhotic-HCC. Conclusions BCP T1762/A1764 mutations are associated wit

关 键 词：乙型肝炎病毒 突变 癌 肝细胞 肝硬变 乙型肝炎E抗原 

分 类 号：R735[医药卫生—肿瘤] R51[医药卫生—临床医学]