Hepatitis B 1762T/1764A mutations, hepatitis C infection, and codon 249 p53 mutations in hepatocellular carcinomas from Thailand
Hepatitis B 1762T/1764A mutations, hepatitis C infection, and codon 249 p53 mutations in hepatocellular carcinomas from Thailand
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DOI：
10.1158/1055-9965.epi-04-0380
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发表时间：
2005-02-01
影响因子：
3.8
通讯作者：
Groopman, JD
中科院分区：
文献类型：
--
作者：
Kuang, SY;Lekawanvijit, S;Groopman, JD
肝细胞癌是全球癌症死亡的主要原因之一。肝癌的病因是多因素的，感染B型肝炎病毒（HBV），其发病机制因获得加速致癌的突变而加剧，或感染丙型肝炎病毒（HCV）和饮食暴露于黄曲霉毒素B-1都有助于提高患这种疾病的风险。在这项研究中，我们试图通过测量34例HCC患者和68例年龄和性别匹配的对照组以及来自泰国北方的25例肝肿瘤患者血浆中HBV 1762（T）/1764（A）双突变、黄曲霉毒素特异性p53基因249（G-->T）突变和HCV的发生率来确定这些药物的作用。总共有14例病例、5例对照和19例肿瘤具有可检测水平的HBV DNA。14例患者、2例对照（2.9%）和17例肿瘤（89.5%）HBV双突变均为阳性。9例（26.5%）、10例对照（14.7%）和6例肿瘤（24%）p53突变阳性。5例（14.7%），无对照，4例肿瘤（16%）有两种突变。这5例病例中诊断为HCC的中位年龄为34岁，而其他病例为51岁。5例（14.7%）和1例（1.5%）HCV酶免疫检测阳性。因此，特定的HBV、HCV和黄曲霉毒素生物标志物揭示了泰国北方HCC发病风险的复杂性，并建议进一步应用这些生物标志物作为预防、干预试验和病因学研究的中间终点。
Hepatocellular carcinoma is one of the leading causes of cancer death worldwide. The etiology of liver cancer is multifactorial, and infection with hepatitis B virus (HBV), whose pathogenesis is exacerbated by the acquisition of mutations that accelerate carcinogenesis, or hepatitis C virus (HCV) and dietary exposure to aflatoxin B-1 all contribute to elevating one's risk for this disease. In this study, we sought to determine the contributions of these agents by measuring the occurrence of an HBV 1762(T)/1764(A) double mutation, an aflatoxin-specific 249(G-->T) mutation of the p53 gene, and HCV in plasma of 34 HCC cases and 68 age- and gender-matched controls, and in 25 liver tumors from northern Thailand. In total, 14 cases, 5 controls, and 19 tumors had detectable levels of HBV DNA. All 14 cases, 2 controls (2.9%), and 17 tumors (89.5%) were positive for the HBV double mutation. Nine cases (26.5%), 10 controls (14.7%), and 6 tumors (24%) were positive for the p53 mutation. Five cases (14.7%), no controls, and 4 tumors (16%) had both mutations. The median age of HCC diagnosis in these 5 cases was 34 years versus 51 years for other cases. Five cases (14.7%) and 1 control (1.5%) were HCV enzyme immunoassay positive. Thus, specific HBV, HCV, and aflatoxin biomarkers reveal the complexity of risks contributing to HCC in northern Thailand and suggest further application of these biomarkers as intermediate end points in prevention, intervention trials, and etiologic investigations.