广西扶绥县肝癌高发区 HBV－DNA 前 S 区变异与肝癌相关性研究

摘要

Objective To investigate the relationship between HBV-DNA Pre-S mutation and the occurrence of hepatocellular carcinoma (HCC) among patients with HBV-related HCC in high-risk region of HCC in Fusui County,Guangxi.Methods A case-control study was performed in 50 patients with HBV-related HCC(HCC group) and 50 chronic HBV carriers(control group).The serum HBV-DNA was extracted from the subjects.Nested PCR was applied to Pre-S amplification.DNA sequencing was performed to analyze the nucleic acid mutation.Results The rates of Pre-S deletion,Pre-S2 start codon mutation and T53C mutation in HCC patients were 38.0%(19 /50), 38.0%(19/50) and 32.0%(16/50),respectively,which were significantly higher than the controls(14.0%(7/50),10.0%(5/50) and 4.0%(2/50),respectively,P <0.05).There were 26 Pre-S deletion cases(69.2%),mainly of TypeⅡdeletion,24 in-frame deletion cases (92.3%) and 23 Pre-S2 5′end deletion cases(88.5%) in two groups.Multivariate unconditional logistic regression analysis revealed that Pre-S deletion,Pre-S2 start codon mutation and T53C mutation were the independent risk factors for the occurrence of HCC(P <0.05). Conclusion HBV-DNA Pre-S deletion,Pre-S2 start codon mutation and T53C mutation closely correlate with the occurrence of HCC in Fusui County,Guangxi.%目的：探讨广西扶绥县肝癌高发区 HBV 相关肝癌患者 HBV－DNA 前 S 区（ Pre－S 区）变异与肝癌发生的关系。方法采用病例对照研究的方法，选择 HBV 相关肝癌患者50例（肝癌组），HBV 慢性携带者50例（对照组），提取受试者血清 HBV－DNA，采用巢式 PCR 的方法扩增 Pre－S 区，测序并分析其核酸变异的情况。结果肝癌组患者 Pre－S 区缺失率、Pre－S2起始密码子变异率、T53C 变异率分别为38．0％（19／50）、38．0％（19／50）和32．0％（16／50），均高于对照组的14．0％（7／50）、10．0％（5／50），4．0％（2／50）（P ＜0．05）。两组发生 Pre－S 区缺失26例，主要为Ⅱ类缺失，占69．2％；框内缺失24例占92．3％；Pre－S25′端缺失23例占88．5％。多因素非条件 logistic 分析结果显示，Pre－S 区缺失、Pre－S2起始密码子变异以及 T53C 变异是肝癌发生的独立危险因素（P ＜0．05）。结论HBV－DNA Pre－S 区缺失、Pre－S2起始密码子变异和 T53C 变异与广西扶绥县 HBV 相关肝癌的发生密切相关。