Abedi-Ardekani Behnoush, Gouas Doriane, Villar Stephanie, Sotoudeh Masoud, Hainaut Pierre
Mechanisms of Carcinogenesis Section, Molecular Carcinogenesis Group, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon, France.
Hepat Res Treat. 2011;2011:475965. doi: 10.1155/2011/475965. Epub 2011 Aug 17.
High incidence of HCC is mostly due to the combination of two major risk factors, chronic infection with hepatitis B (HBV) and/or C (HCV) viruses and exposure to the mycotoxin aflatoxin B(1), which induces a particular mutation at codon 249 in TP53 (R249S). Eight genotypes of HBV are diversely found in high and low incidence areas. Regardless of documented strong associations between TP53 R249S mutation and HBV genotypes B, C, A or E, there is no report of such association for genotype D despite of the presence of aflatoxin in areas with high prevalence of HBV genotype D. In Iran, 3% of the population is chronically infected with HBV, predominantly genotype D. Twenty-one histologically confirmed HCC cases from Iran were analyzed for TP53 R249S and HBV double mutations 1762(T)/1764(A), hallmarks of more pathogenic forms of HBV. We did not detect any of these mutations. In addition, we report the only case identified so far carrying both R249S mutation and chronic HBV genotype D, a patient from The Gambia in West Africa. This paper suggests that association between HBV genotype D and aflatoxin-induced TP53 mutation is uncommon, explaining the relatively lower incidence of HCC in areas where genotype D is highly prevalent.
肝癌的高发病率主要归因于两个主要风险因素的共同作用，即慢性感染乙型肝炎病毒（HBV）和/或丙型肝炎病毒（HCV）以及接触霉菌毒素黄曲霉毒素B1，后者会在TP53基因的第249密码子处诱发特定突变（R249S）。在肝癌高发病率和低发病率地区发现了8种不同的HBV基因型。尽管有文献记载TP53 R249S突变与HBV基因型B、C、A或E之间存在密切关联，但在HBV基因型D高流行地区，尽管存在黄曲霉毒素，却没有关于该基因型这种关联的报告。在伊朗，3%的人口慢性感染HBV，主要是基因型D。对来自伊朗的21例经组织学确诊的肝癌病例进行了TP53 R249S和HBV双突变1762(T)/1764(A)分析，这是更具致病性的HBV形式的标志。我们未检测到任何这些突变。此外，我们报告了迄今为止唯一一例同时携带R249S突变和慢性HBV基因型D的病例，该患者来自西非的冈比亚。本文表明，HBV基因型D与黄曲霉毒素诱导的TP53突变之间的关联并不常见，这解释了在基因型D高度流行的地区肝癌发病率相对较低的原因。
