International Agency for Research on Cancer, Molecular Carcinogenesis Group, Lyon, France.
Carcinogenesis. 2012 Jun;33(6):1219-24. doi: 10.1093/carcin/bgs068.
In regions with high prevalence of chronic hepatitis B virus (HBV) infection and dietary aflatoxin B(1) (AFB(1)) exposure, hepatocellular carcinomas (HCCs) often contain TP53 mutation at codon 249 (R249S). Furthermore, a C-terminal truncated HBx protein expressed from hepatocyte integrated HBV is associated with HCC development. This study evaluates the association between R249S and HBX status in relation to HCC in West African population. HBX (complete or 3'-truncated) and HBS genes were assessed by PCR in cell-free DNA (CFDNA) from plasma of subjects recruited in a hospital-based case-control study (325 controls, 78 cirrhotic patients and 198 HCC cases) conducted in The Gambia. These samples had been previously analyzed for R249S and HBV serological status. Complete HBX sequence was frequently detected in CFDNA of HCC-R249S positive (77%, 43/56) compared with HCC-R249S-negative cases (44%, 22/50). Conversely, the proportion of 3'-truncated HBX gene was significantly higher in HCC-R249S negative than positive cases (34%, 17/50, compared with 12%, 7/56) (χ(2) = 12.12; P = 0.002; distribution of R249S negative and positive according to HBX status). Occult HBV infection (detected by PCR) was present in 24% of HCC previously considered as negative by HBV serology. Moreover, HBV mutation analysis revealed that double mutation at nucleotides 1762(T)/1764(A) was associated with diagnosis of cirrhosis or HCC {cirrhosis: odds ratio (OR): 9.50 [95% confidence interval (CI) 1.50-60.11]; HCC: OR: 11.29 [95% CI 2.07-61.47]}. These findings suggest that in HCC from The Gambia, complete HBX sequences are often associated with the presence of TP53 R249S mutation.
在慢性乙型肝炎病毒（HBV）感染和黄曲霉毒素 B1（AFB1）暴露流行的地区，肝细胞癌（HCC）通常含有密码子 249（R249S）的 TP53 突变。此外，来自整合了 HBV 的肝细胞表达的 C 端截断的 HBx 蛋白与 HCC 的发展有关。本研究评估了 R249S 与 HBX 状态与西非人群 HCC 之间的关联。在冈比亚进行的一项基于医院的病例对照研究（325 名对照、78 名肝硬化患者和 198 名 HCC 患者）中，通过聚合酶链反应（PCR）在血浆无细胞 DNA（cfDNA）中评估 HBX（完整或 3'-截断）和 HBS 基因。这些样本之前已经分析了 R249S 和 HBV 血清学状态。在 HCC-R249S 阳性（77%，43/56）与 HCC-R249S 阴性病例（44%，22/50）相比，cfDNA 中经常检测到完整的 HBX 序列。相反，在 HCC-R249S 阴性病例中，3'-截断的 HBX 基因的比例明显高于阳性病例（34%，17/50，而 12%，7/56）（χ(2) = 12.12；P = 0.002；根据 HBX 状态的 R249S 阴性和阳性分布）。先前通过 HBV 血清学检测为阴性的 HCC 中，存在 24%的隐匿性 HBV 感染（通过 PCR 检测）。此外，HBV 突变分析显示，核苷酸 1762（T）/1764（A）的双重突变与肝硬化或 HCC 的诊断相关（肝硬化：比值比（OR）：9.50 [95%置信区间（CI）1.50-60.11]；HCC：OR：11.29 [95% CI 2.07-61.47]）。这些发现表明，在冈比亚的 HCC 中，完整的 HBX 序列通常与 TP53 R249S 突变的存在相关。
