Specific mutations in enhancer II/core promoter of hepatitis B virus subgenotypes C1/C2 increase the risk of hepatocellular carcinoma
Specific mutations in enhancer II/core promoter of hepatitis B virus subgenotypes C1/C2 increase the risk of hepatocellular carcinoma
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DOI：
10.1016/j.jhep.2006.06.018
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发表时间：
2006-11-01
影响因子：
25.7
通讯作者：
Mizokami, Masashi
中科院分区：
文献类型：
--
作者：
Tanaka, Yasuhito;Mukaide, Motokazu;Mizokami, Masashi
背景/目标：B型肝炎病毒C基因型（HBV/C）可分为两个不同的亚型：HBV/C1/Cs（东南亚）和HBV/C2/Ce方法：在118名携带者的匹配横断面对照研究中，评估了各亚型之间增强子II/核心启动子和前核心区的病毒差异及其与肝细胞癌（HCC）的相关性（来自香港）HBV/C1/Cs（48.0岁，81%男性，40% HBeAg+，44% HCC）和210例HBV/C2/Ce（172来自日本，38来自香港）（50.2岁，78%男性，30% HBeAg+，46% HCC）。单因素分析显示V1753突变是HBeAg阳性Cl/Cs携带者发生HCC的预测因子HBeAg阳性C2/Ce携带者中T1653、V1753、T1762/A1764与HBeAg阴性C2/Ce携带者比较，差异有统计学意义（P < 0.05）。在所有HBV/C受试者的多变量分析中，HCC的独立预测因素是C2/Ce亚型（比值比，4.21; 95%置信区间，1.07-16.23），T1653（3.64; 1.93-6.86），V1753（3.07; 1.66-5.65）和T1762/A1764（2.58; 1.21-5.49）突变，年龄（>= 50岁）、性别（男性）和HBeAg结论：我们的数据表明，T1653和/或V1753突变除了T1762/A1764之外，在HBV/Cl中HBeAg状态的背景下与HCC的相关性不同。Cs和C2/Ce载体。HBV/C亚型具有特异性的突变模式，这可能是HBV/C2/Ce致癌性增加的原因。(c)2006年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: Hepatitis B virus genotype C (HBV/C) has been classified into two geographically distinct subgcnotypes; HBV/C1/Cs (Southeast Asia) and HBV/C2/Ce (East Asia).Methods: Viral differences in enhancer II/core promoter and precore regions between the subgenotypes and their association with hepatocellular carcinoma (HCC) were assessed in a matched cross-sectional control study of 118 carriers (from Hong Kong) with HBV/C1/Cs (48.0 years, 81% male, 40% HBeAg+, 44% HCC) and 210 HBV/C2/Ce (172 from Japan, 38 from Hong Kong) (50.2 years, 78% male, 30% HBeAg+, 46% HCC).Results: Univariate analyses showed that mutation V1753 was predictive for HCC among HBeAg-positive-Cl/Cs-carriers (P = 0.0055), and T1653 among HBeAg-positive-C2/Ce-carriers (P = 0.018), and T1653 or V1753 or T1762/A1764 among HBeAg-negative-C2/Ce-carriers (P < 0.05). In the multivariate analysis on all HBV/C subjects, independent predictive factors for HCC were subgenotype C2/Ce (odds ratio, 4.21; 95% confidence interval, 1.07-16.23), T1653 (3.64; 1.93-6.86), V1753 (3.07; 1.66-5.65) and T1762/A1764 (2.58; 1.21-5.49) mutations, age (>= 50 years), gender (male) and HBeAg (positive).Conclusions: Our data indicate that T1653 and/or V1753 mutations in addition to T1762/A1764 are differently associated with HCC in context of HBeAg status among HBV/Cl/Cs and C2/Ce-carriers. HBV/C subgenotypes have specific mutation patterns, which is probably responsible for increased carcinogenesis of HBV/C2/Ce. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.