Association of hepatitis B virus pre-S deletions with the development of hepatocellular carcinoma in Qidong, China.
Association of hepatitis B virus pre-S deletions with the development of hepatocellular carcinoma in Qidong, China.
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DOI：
10.1371/journal.pone.0098257
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Lu CH
中科院分区：
文献类型：
--
作者：
Qu LS;Liu JX;Liu TT;Shen XZ;Chen TY;Ni ZP;Lu CH
探讨B型肝炎病毒（HBV）前S区和S区基因突变在启东地区肝细胞癌（HCC）发生发展中的作用。我们对1996年8月招募的2387名男性HBV携带者进行了年龄匹配的病例对照研究。对96例肝癌患者和97例正常对照者进行了HBV前S/S区序列测定。此外，我们还收集了11例HCC患者的一系列连续样本，以评估HCC发生前后的前S缺失模式。校正年龄、吸烟史和饮酒史后，HBeAg阳性、前S缺失、前S2起始密码子突变和T53 C突变与HCC显著相关，校正比值比（OR）为1.914 - 3.199。肝癌患者前S2基因T31 C突变频率低于对照组（0.524; 95%CI 0.280-0.982）。HBV前S区缺失主要集中在前S2区的5′端。多因素分析显示前S区缺失和前S2区起始密码子突变是肝癌的独立危险因素。OR（95%CI）分别为2.434（1.063-5.573）和3.065（1.099-8.547）。纵向观察表明，HBV感染初期前S区缺失突变并非获得性，而是在肝病的长期病程中发生的。前S缺失和前S2起始密码子突变与HCC的发生独立相关。结果还提供了直接证据，即前S缺失突变不是从感染开始获得的，而是在肝脏疾病进展过程中重新出现的。
To investigate the roles of mutations in pre-S and S regions of hepatitis B virus (HBV) on the progression of hepatocellular carcinoma (HCC) in Qidong, China. We conducted an age matched case-control study within a cohort of 2387 male HBV carriers who were recruited from August, 1996. The HBV DNA sequence in pre-S/S regions was successfully determined in 96 HCC cases and 97 control subjects. In addition, a consecutive series of samples from 11 HCC cases were employed to evaluate the pre-S deletion patterns before and after the occurrence of HCC. After adjustment for age, history of cigarette smoking and alcohol consumption, HBeAg positivity, pre-S deletions, pre-S2 start codon mutations, and T53C mutation were significantly associated with HCC, showing adjusted odds ratios (ORs) from 1.914 to 3.199. HCC patients also had a lower frequency of T31C mutation in pre-S2 gene, compared with control subjects (0.524; 95% CI 0.280-0.982). HBV pre-S deletions were clustered mainly in the 5′ end of pre-S2 region. Multivariate analysis showed that pre-S deletions and pre-S2 start codon mutations were independent risk factors for HCC. The OR (95% CI) were 2.434 (1.063–5.573) and 3.065 (1.099–8.547), respectively. The longitudinal observation indicated that the pre-S deletion mutations were not acquired at the beginning of HBV infection, but that the mutations occurred during the long course of liver disease. Pre-S deletions and pre-S2 start codon mutations were independently associated with the development of HCC. The results also provided direct evidence that pre-S deletion mutations were not acquired from the beginning of infection but arose de novo during the progression of liver disease.
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