乙型肝炎病毒反转录酶编码区核苷酸变异与肝癌的相关性研究  

The association between mutations in the reverse transcriptase domain of hepatitis B virus polymerase gene with tumorigenesis of hepatocellular carcinoma

作　　者：高付敏 吴燕[2] 赵芝梅[2] 金晏[2] 钱耕荪[2] 陈陶阳[3] 张亚玮[3] 王金兵[3] 甘愉[2] 项永兵[4] 屠红[2] 

机构地区：[1]复旦大学公共卫生学院流行病学教研室,上海200032 [2]上海交通大学附属仁济医院上海市肿瘤研究所癌基因及相关基因国家重点实验室,上海200032 [3]启东市人民医院/启东肝癌防治研究所病因室,江苏启东226200 [4]上海交通大学附属仁济医院上海市肿瘤研究所流行病室,上海200032

出　　处：《肿瘤》2014年第2期141-146,共6页Tumor

基　　金：传染病国家重大专项基金资助项目(编号:2012ZX10002-008-002)

摘　　要：目的：探讨乙型肝炎病毒（hepatitisBvirus，HBy）一多聚酶（polymerase，P）基因反转录酶（reversetranscriptase，RT）区突变与肝癌发生的关系。方法：收集202例肝癌患者及202例年龄、性别匹配的慢性HBV携带者（对照组）的血清，采用病例一对照的方法进行研究；PCR法扩增HBV-P基因的RT区，对扩增产物直接测序并进行序列分析，探讨该区域基因突变与肝癌发生的关系。结果：HBIT-P基因RT区共有3个位点发生突变T895A、A904T和C955T，它们在肝癌组中的发生率均显著高于对照组，分别为47．5％坩37．1％（P=0．034）、5．4％VS1．0％（P=0．011）和5．4％vs1．5％（P=O．030）。Logistic多因素分析结果显示，T895A是肝癌的独立危险因素[比值比（oddsratio，0R）=2．230，95％可信区间（confidenceinterval，CI）：1．230～4．044，P=0．008]。A904T和C955T虽有增加肝癌风险的趋势（OR=6．523，95％CI：0．838～50．733和OR=2．904，95％C7：0．599～14．093），但差异无统计学意义。然而，A904T和C955T中有一项为阳性的发生率在肝癌组和对照组中分别是9．4％和2．5％（P=0．003），经多因素调整后统计显示，与肝癌具有相关性（OR=4．145，95％CI：1．170～14．681，P=0．028）。结论：邯V-P基因RT区存在着与肝癌发生相关的突变。Objective： To explore the relationship between the mutations in the reverse transcriptase （RT） domain of hepatitis B virus polymerase （HBV-P） gene and the occurrence and development of hepatocellular carcinoma （HCC）. Methods： In this case-control study, the serum samples from 202 HCC patients and 202 chronic hepatitis B virus （CHB） carriers matching for age and gender were collected. The sequence of the RT domain of HBV-P gene was determined by direct sequencing following PCR amplification. The relationship between the mutations in the RT domain of HBV-P gene and the occurrence and development of HCC was analyzed. Results： The T895A, A904T and C955T mutations in the RT domain of HBV-P gene were all significantly associated with HCC compared to non-HCC controls （P = 0.034, 47.5% vs 37.1%; P = 0.011, 5.4% vs 1.0%; P = 0.030, 5.4% vs 1.5%）. Furthermore, the Logistic multivariate analysis showed that T895A was an independent risk factor for HCC [odds ratio （OR） = 2.230, 95% confidence interval （CI）： 1.230-4.044, P = 0.008]. A904T or C955T increased the risk of HCC occurrence either （OR = 6.523, 95% CI： 0.838-50.733; OR = 2.904,95% CI： 0.599-14.093）, but it did not reach statistical significance. The mutation rate of combined mutation occurrence either in A904 or C955T was 9.4% in HCC group and 2.5% in non-HCC controls （P = 0.003）. The adjusted OR was 4.145 （95% CI： 1.170-14.681）, demonstrating its significant association with HCC （P = 0.028）. Conclusion： The mutations in the RT domain ofHBV-P qene are associated with the tumorigenesis of HCC.

关 键 词：肝肿瘤 肝炎病毒 乙型 DNA突变分析 流行病学方法 

分 类 号：R735.7[医药卫生—肿瘤]