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目的研究广东汉族肝癌HBV基因型、基本核心启动子(BCP)/前C区突变与肝癌易感性的相关关系。方法按照病例对照研究设计方法,纳入HBV合并肝癌患者(病例组)100例和HBV携带者(对照组)100例,收集血清样本,提取HBV DNA,采用巢式PCR扩增HBV S区、BCP及前C区片段,双向测序,分析HBV基因型、BCP/前C区基因突变与HBV合并肝癌易感性的相关性。结果病例组BCP区A1762T/G1764A突变及前C区T1858C突变高于对照组,分别为92.0%和73.0%(P<0.05)、52.0%和32.0%(P<0.05);对照组A1775G突变发生率高于病例组,分别为31.0%和14.0%(P<0.05)。多因素Logistic回归分析显示,HBV BCP区A1762T/G1764A突变和前C区T1858C突变与HBV合并肝癌发生独立相关[OR 6.508(95%CI:1.287~16.739,P<0.05)和3.371(95%CI:2.268~8.163,P<0.05)];而BCP区A1775G突变则为保护因素[OR=0.163(95%CI:0.043~0.489,P<0.05)]。结论 HBV C基因型是广东深圳地区HBV合并肝癌的主要流行株,HBV BCP区A1762T、G1764A、A1775G、前C区T1858C基因多态性与HBV合并肝癌的易感性具有密切关系。
Objective To study the relationship between HBV genotype, basic core promoter (BCP) / precore mutation and liver cancer susceptibility in Han Chinese patients with hepatocellular carcinoma in Guangdong province. Methods According to the case-control study design method, 100 patients with HBV-associated hepatocellular carcinoma (case group) and 100 HBV carriers (control group) were enrolled. Serum samples were collected and HBV DNA was extracted. Pre-C region fragment, two-way sequencing, analysis of HBV genotype, BCP / pre-C gene mutations and HBV associated liver cancer susceptibility. Results The A1762T / G1764A mutation in the BCP region and the T1858C mutation in the pre-C region were significantly higher in the BCP group than those in the control group (92.0% vs 73.0%, P <0.05), 52.0% and 32.0% (P <0.05) Higher than the case group, respectively, 31.0% and 14.0% (P <0.05). Multivariate Logistic regression analysis showed that A1762T / G1764A mutation in HBV BCP region and T1858C mutation in pre-C region were independently associated with HBV-associated hepatocellular carcinoma (OR 6.508, 95% CI: 1.287-16.739, P <0.05) and 3.371 2.268 ~ 8.163, P <0.05). The A1775G mutation in BCP area was protective factor [OR = 0.163 (95% CI: 0.043-0.489, P <0.05)]. Conclusion HBV C genotype is the main epidemic strain of HBV combined with HCC in Shenzhen, Guangdong Province. The polymorphisms of A1762T, G1764A, A1775G and pre-C region T1858C in HBV BCP are closely related to the susceptibility of HBV with HCC.