乙肝病毒基因型及基因变异与原发性肝癌的相关性

The correlation of HBV genotypes and gene-mutants with primary hepatic carcinoma

目的分析HBV基因型及基因变异与原发性肝癌(PHC)发病的关系。方法采用基因型特异引物PCR法测定HBV基因型,限制性酶切片段长度多态性检测基因亚型;直接测序法检测HBV DNA 1653、1762/1764及1896位点的变异情况;统计比较多个因素在慢性乙型肝炎(CHB)和PHC患者中的异同,并进行危险因素分析。结果与CHB组比较,PHC组患者年龄较大,HBeAg阴性更常见,而ALT水平和HBV DNA载量较低(P<0.05)。CHB组HBV的基因型B型与C型相当,而PHC组绝大多数为C型(P<0.01);两组基因型C型的亚型多为Ce亚型。两组病毒G1896A变异无差异,而PHC组C1653T、A1762G/T1764A变异出现的几率较高(P<0.05)。Logistic回归分析表明只有基因C型和高龄为PHC的独立危险因素。结论 HBV基因型C型为HBV相关PHC发病的独立危险因素;C1653T、A1762G/T1764A变异与PHC有一定相关,但非独立危险因素。

Objective To analyze the relationship of HBV genotypes and gene-mutants with primary hepatic carcinoma（PHC）.Methods Serum samples were collected from 177 HBV DNA positive patients,of whom 94 cases were with chronic hepatitis B（group CHB） and 83 cases with PHC（group PHC）.The genotypes were determined by PCR using type-specific primers,and the subgenotypes of hepatitis B virus genotype C （HBV/C） were assayed by restriction fragment length polymporphism.The mutants of C1653T,A1762T/G1764A and G1896A were tested by direct sequencing.The risk factors were statistically analyzed.Results Compared to group CHB,the patients in group PHC were older with more e-antigen negative rate,but lower ALT level and HBV DNA loading（P0.05）.The genotype B was almost similar to genotype C in group CHB,while genotype C accounted for the majority in group PHC（P0.01）.The dominant subgenotype of HBV/C was Ce in both groups.Compared with HBV/CHB,HBV/PHC had more C1653T and A1762T/G1764A mutants（P0.05）,but G1896A mutant was not significantly different between two groups.Genotype C and age were the independent risk factors for PHC（OR=11.566 and OR=2.370,respectively）.Conclusion Genotype C is an independent risk factor for HBV-associated PHC.C1653T and A1762T/G1764A mutants have relations with PHC,but they are not independent risk factors.