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首页> 外文期刊>Cancer epidemiology, biomarkers and prevention: A publication of the American Association for Cancer Research >TP53 R249S mutations, exposure to aflatoxin, and occurrence of hepatocellular carcinoma in a cohort of chronic hepatitis B virus carriers from Qidong, China.
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TP53 R249S mutations, exposure to aflatoxin, and occurrence of hepatocellular carcinoma in a cohort of chronic hepatitis B virus carriers from Qidong, China.

机译：一组来自中国启东的慢性乙型肝炎病毒携带者中的TP53 R249S突变，黄曲霉毒素暴露和肝细胞癌的发生。

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摘要

Hepatocellular carcinoma (HCC) has a high mortality in East Asia and Sub-Saharan Africa, two regions where the main etiologic factors are chronic infections with hepatitis B virus and dietary exposure to aflatoxin. A single base substitution at the third nucleotide of codon 249 of TP53 (R249S) is common in HCC in these regions and has been associated with aflatoxin-DNA adducts. To determine whether R249S may be detected in plasma DNA before HCC diagnosis, we conducted a case-control study nested in a cohort of adult chronic hepatitis B virus carriers from Qidong County, People's Republic of China. Of the 234 plasma specimens that yielded adequate DNA, only 2 (0.9%) were positive for R249S by restriction fragment length polymorphisms, and both of them were controls. Of the 249 subjects tested for aflatoxin-albumin adducts, 168 (67%) were positive, with equal distribution between cases and controls. Aflatoxin-albumin adduct levels were low in the study, suggesting an overall low ongoing exposure to aflatoxin in this cohort. The R249S mutation was detected in 11 of 18 (61%) available tumor tissues. To assess whether low levels of mutant DNA were detectable in pre-diagnosis plasma, 14 plasma specimens from these patients were analyzed by short oligonucleotide mass analysis. Nine of them (64%) were found to be positive. Overall, these results suggest that HCC containing R249S can occur in the absence of significant recent exposure to aflatoxins. The use of short oligonucleotide mass analysis in the context of low ongoing aflatoxin exposure may allow the detection of R249S in plasma several months ahead of clinical diagnosis.
机译：肝细胞癌（HCC）在东亚和撒哈拉以南非洲这两个地区的死亡率很高，这两个地区的主要病因是乙型肝炎病毒的慢性感染和饮食中黄曲霉毒素的暴露。在这些区域的HCC中，TP53（R249S）密码子249的第三个核苷酸处的单碱基取代是常见的，并与黄曲霉毒素-DNA加合物相关。为了确定在HCC诊断之前是否可以在血浆DNA中检测到R249S，我们进行了一项病例对照研究，该研究嵌套在来自中国启东县的成年慢性乙型肝炎病毒携带者队列中。在234个产生足够DNA的血浆样本中，通过限制性片段长度多态性，仅2个（0.9％）的R249S呈阳性，并且它们均为对照。在249位接受黄曲霉毒素-白蛋白加合物检测的受试者中，有168位（67％）呈阳性，病例与对照组之间的分布相等。该研究中的黄曲霉毒素-白蛋白加合物水平较低，表明该人群中黄曲霉毒素的总体持续暴露水平较低。在18个可用肿瘤组织中的11个（61％）中检测到R249S突变。为了评估在预诊断血浆中是否检测到低水平的突变体DNA，通过简短的寡核苷酸质量分析对这些患者的14个血浆标本进行了分析。他们中有9人（占64％）为阳性。总体而言，这些结果表明，在近期没有大量暴露于黄曲霉毒素的情况下，可能会发生含有H249的HCC。在低黄曲霉毒素持续暴露的情况下使用短寡核苷酸质量分析可以在临床诊断前数月检测血浆中的R249S。

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