249ser TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma
249ser TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma
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DOI：
10.1038/sj.onc.1208732
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发表时间：
2005-09-01
期刊：
影响因子：
8
通讯作者：
Montesano, R
中科院分区：
文献类型：
--
作者：
Kirk, GD;Lesi, OA;Montesano, R
来自高黄曲霉毒素饮食暴露和B肝炎病毒（HBV）流行地区的肝细胞癌（HCC）通常在TP 53的密码子249处含有特异性突变（249（ser）; AGG至AGT，Arg至Ser）。这种突变也可在来自这些地区的HCC患者和健康受试者的血浆的循环无细胞DNA中检测到。我们在一项病例对照研究设计中研究了血浆249（ser）和HBV感染的联合作用，该研究涉及来自西非冈比亚的348名对照、98名疟疾患者和186名HCC参与者，该地区HCC发病率较高。在3.5%的对照组、15.3%的肝硬化组和39.8%的HCC病例中检测到249（ser）突变（肝硬化的校正比值比（OR）：4.83（95%置信区间（CI）：1.71-13.7），HCC的校正比值比（OR）：20.3（8.19-50.0））。在45/183例（24.6%）HCC病例中观察到HBsAg阳性沿着血浆249（ser），而对照组仅为1例（0.3%）。HCC的风险与单独HBV标志物（OR：10.0，95% CI：5.16-19.6）、单独249（ser）标志物（OR：13.2，95% CI：4.99-35.0）以及两种标志物均存在（OR：399，95% CI：48.6-3270）相关。这些结果表明，黄曲霉毒素对TP 53的突变效应对HCC风险产生倍增效应，如通过检测血浆249（ser）监测的，伴随HBV慢性感染。
Hepatocellular carcinoma (HCC) from regions with high dietary exposure to aflatoxins and endemic for hepatitis B virus (HBV) often contain a specific mutation at codon 249 in TP53 (249(ser); AGG to AGT, Arg to Ser). This mutation is also detectable in circulating cell-free DNA from the plasma of HCC patients and healthy subjects in these regions. We have examined the joint effect of plasma 249(ser) and HBV infection in a case-control study design involving 348 control, 98 cirrhotic, and 186 HCC participants from The Gambia, West Africa, an area of high HCC incidence. The 249(ser) mutation was detected in 3.5% of controls, 15.3% of cirrhotics, and 39.8% of HCC cases (adjusted odds ratios (OR): 4.83, (95% confidence interval (CI): 1.71-13.7) for cirrhosis and 20.3 (8.19-50.0) for HCC). HBsAg positivity along with plasma 249(ser) was observed in 45/183 (24.6%) HCC cases compared to only one (0.3%) control. Risk for HCC was associated with markers of HBV alone (OR: 10.0, 95% CI: 5.16-19.6), 249(ser) alone (OR: 13.2, 95% CI: 4.99-35.0), and both markers present (OR: 399, 95% CI: 48.6-3270). These results suggest a multiplicative effect on HCC risk resulting from the mutational effect of aflatoxin on TP53, as monitored by detection of plasma 249(ser), with concomitant chronic infection with HBV.