广西原发性肝细胞癌黄曲霉毒素B_1-DNA加合物表达及p53第249密码子突变分析  

Detection of aflatoxin B_1-DNA adducts and mutation of gene p53 codon 249 in hepatocellular carcinoma in Guangxi of China

作　　者：伍国俊[1] 黎乐群[2] 彭涛[3] 

机构地区：[1]广西医科大学研究生学院,南宁530021 [2]广西医科大学附属肿瘤医院,南宁530021 [3]广西医科大学第一附属医院肝胆血管外科,南宁530021

出　　处：《中国癌症防治杂志》2010年第4期249-254,共6页CHINESE JOURNAL OF ONCOLOGY PREVENTION AND TREATMENT

基　　金：国家自然科学基金资助项目(30960021);广西科学研究与技术开发计划资助项目(桂科基0731064);广西医疗卫生重点科研资助课题(重20085)

摘　　要：目的通过研究广西地区肝癌患者中黄曲霉毒素B1(Aflatoxin B1,AFB1)-DNA加合物的表达和p53第249密码子突变情况及其关系,探讨AFB1长期暴露与人群原发性肝细胞癌(hepatocellular carcinoma,HCC)发生的关系。方法实验组为广西医科大学第一附属医院肝胆外科收治的63例HCC患者行根治性手术切除的肝肿瘤组织。按肿瘤大小分为小肝癌组(≤5cm)和大肝癌组(>5cm),同时小肝癌组包括两个亚组Ⅰ组(≤3cm)和Ⅱ组(>3cm)。另取10例来自肝移植供肝及肝外伤切除的正常肝组织作为正常对照组。通过免疫组织化学(immunohistochemistry,IHC)法检测各组样本AFB1-DNA加合物的表达,并以PCR结合直接测序的方法检测其p53第249密码子的突变情况。结果小肝癌组的AFB1-DNA加合物阳性率最高(73.8%),显著高于大肝癌组(P=0.016)。而小肝癌组p53第249密码子的突变率(35.7%)却显著低于大肝癌组(P=0.007)。正常对照组AFB1-DNA加合物阳性率为50.0%,但未发现p53第249密码子存在突变。Ⅰ组与Ⅱ组之间无论是AFB1-DNA加合物阳性率还是p53第249密码子的突变率差异均无统计学意义(P1=0.676,P2=1.000)。实验组中,33.3%的样本为AFB1-DNA加合物和p53第249密码子突变双阳性,22.2%的样本为AFB1-DNA加合物和第249密码子突变双阴性。结论广西为AFB1高污染地区,正常人群普遍存在AFB1的暴露。AFB1的暴露可增加HCC的发病概率。p53第249密码子突变可能是影响AFB1相关HCC发生、发展的因素。结合AFB1-DNA加合物表达和第249密码子突变的情况,可有效地了解肝癌患者长期持续性或非持续性的AFB1暴露下DNA的累积损伤情况。Objective To explore the association between chronic AFB1 exposure and development of hepatocellular carcinoma（HCC）.Methods HCC tissues from 63 patients underwent radical resection in this department were included for the study.The samples were categorized into small HCC（SHCC）group（≤5cm）and big HCC（BHCC）group（5cm）according to the tumor size.The SHCC group included two subgroups named teamⅠ（≤3cm）and teamⅡ（3cm）respectively.The control group included 10 normal liver tissues collected from donors for liver transplantation or patients with liver trauma but without any liver disease.Immunohistochemistry method was used to detect AFB1-DNA adducts,and polymerase chain reaction（PCR）with direct sequencing was applied to study the mutation in codon 249 of p53 gene for all the samples.Results The detectable rate of AFB1-DNA adducts was 73.8% in SHCC group,which was significantly higher than that in BHCC group（P=0.016）.Rate of mutation in codon 249 of p53 in SHCC group was 35.7%,which were significantly lower than that in BHCC group（P=0.007）.The detectable rate of AFB1-DNA adducts in control group was 50%,while no mutation in codon 249 of p53 was found in this group.The detectable rate of AFB1-DNA adducts and codon 249 mutation were not significantly different between team Ⅰand team Ⅱ（P=0.676 and P=1.000 respectively）.The ration of HCC sample with both positive AFB1-DNA adducts and codon 249 mutation was 33.3%,while the ration of HCC sample with both markers negative was 22.2%.Conclusions Universal AFB1 exposure in Guangxi might increase the incidence of HCC in this region.Mutation in codon 249 of p53 might associate with the AFB1-related HCC.The detections of AFB1-DNA adduct and mutation in codon 249 of p53 could help to find out the accumulated damage in host DNA induced by AFB1.

关 键 词：HCC AFB1 DNA加合物 p53第249密码子 突变 

分 类 号：R735.7[医药卫生—肿瘤]