乙型肝炎病毒前S缺失突变与肝癌关系的巢式匹配病例对照研究  

A matched nested case-control study of the relationship between hepatitis B virus pre-S deletion mutations and hepatocellular carcinoma

作　　者：王学燕[1] 李国坚[2] 董柏青[1] 陈钦艳[1] 方孔雄[3] 杨进业[1] 黄坚[3] 韦少超[3] 方钟燎[1] 黄志碧[4] Caroline A Sabin Tim J Harrison 

机构地区：[1]广西壮族自治区疾病预防控制中心,南宁530028 [2]广西壮族自治区卫生厅,南宁530021 [3]广西隆安县疾病预防控制中心,532700 [4]广西医科大学公共卫生学院,南宁530021 [5]英国伦敦大学学院

出　　处：《应用预防医学》2010年第1期5-8,共4页Applied Preventive Medicine

基　　金：英国wellcome基金会资助项目(072058/Z/03/Z)

摘　　要：目的了解乙型肝炎病毒(HBV)前S基因缺失突变是否是肝癌的危险因素以及它的作用是否受HBV核心基因启动子双突变的混淆影响。方法按巢式匹配病例对照研究的方法,从隆安研究队列中选择33对病例(肝癌患者)和对照(HBsAg无症状携带者),配对的条件之一是病例和对照HBV核心基因启动子序列相同,用套式聚合酶链反应(nested PCR)对研究对象血清HBV前S基因扩增和序列分析。结果肝癌患者组前S基因缺失突变率(45.5%,15/33)显著高于对照组(6/33,18.2%)(χ2=7.364,P<0.01);男女间突变率无显著性差异(28%与43.8%,χ2=1.386,P>0.05)。多因素条件logistic回归分析结果显示,前S缺失突变是肝癌的危险因素(危险比为7,95%可信区:0.861-56.894),而HBeAg,抗-HBe及肝功能则与肝癌无关。核心基因启动子双突变组与核心基因启动子野毒株组之间的前S缺失突变率无显著性差异(χ2=0.597,P>0.05)。结论HBV前S缺失突变是肝癌的独立的危险因素,它的发生及作用与核心基因启动子双突变无关。Objectives To determine whether infection with hepatitis B virus （HBV） with pre - S deletions is independently associated with the development of hepatocellular carcinoma （HCC）, without the confounding effects of basal core pmmoter （BCP） double mutations. Methods According to matched nested casecontrol study, 33 paired cases （HCC patients） and controls （HBsAg asymptomatic carriers） was selected from the Long An cohort. The control was matched for the status of BCP sequence （wild type or double mutations）. The pre - S region of HBV in sera from study subjects was amplified with nested PCR and sequenced. Results The prevalence of pre - S deletions was significantly higher in HCC（45.5%, 15 of 33） than the controls （18.2% , 6 of 33） （X^2= 7. 364, P 〈 0.01 ） . There was no significant difference in the prevalence of deletions between males and females （X^2= 1. 386, P 〉 0.05） . On multivariate conditional logistic regression analysis, pre- S deletion remains independently associated with the development of HCC （Hazard Ratio = 7,95% Confidence Limits = 0.861 - 56. 894） but HBeAg, anti - HBe and ALT concentrations were not. related to HCC. There was no significant difference in pre - S deletions between the BCP mutant group and BCP wild type group （X^2= 0. 5974, P 〉 0.05） . Conclusions The pre - S deletions constitute an independent risk factor for HCC and their emergence and effect are in- dependent of BCP mutations.

关 键 词：乙型肝炎病毒 前S基因缺失突变 肝癌 巢式匹配病例对照研究 

分 类 号：R512.62[医药卫生—内科学]