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

Relationship between HBV-DNA Pre-S mutation and hepatocellular carcinoma in high-risk region of hepatocellular carcinoma 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-S2 5'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。

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.