El-Shanawani Faten M, Abdel-Hadi Afaf A, Abu Zikri Nadia B, Ismail Alaa, El-Ansary Mahmoud, El-Raai Ahmed
Department of Clinical Chemistry, Theodore Bilharz Research Institute, Imbaba, Giza, Egypt.
J Egypt Soc Parasitol. 2006 Apr;36(1):221-39.
The incidence of hepatocellular carcinoma (HCC) varies widely worldwide. Chronic infection with hepatitis B virus (HBV) and exposure to aflatoxins in foodstuffs are the main risk factors. AAG to AGT transversion at codon 249 of the P53 gene arg-ser (249ser) has been identified as a hotspot, reflecting DNA damage caused by aflatoxin B1 metabolites in HCC. Because HBV infection is often endemic in high aflatoxin exposure areas, it is still not clear whether HBV acts as a con-founder or as a synergistic partner in the development of the 249ser P53 mutation. Serum levels of soluble interleukin 2 receptor (sIL-2R) correlated with the progression of liver cirrhosis independently of its etiology. This fact may reflect the stimulation of T-lymphocytes, monocytes and macrophages in liver cirrhosis. The inter-relationship among aflatoxin exposure, HBV & HCV infections, P53 & sIL-2R in patients with liver cirrhosis and hepatocellular carcinoma was studied. The results revealed significant increase in serum levels of mutant P53, sIL-2R and aflatoxin B1 in patients with cirrhosis and those with HCC compared to the controls. HCC patients showed levels of all the three parameters significantly higher than both cirrhotics and controls (P<0.001). Correlations were found between serum aflatoxin B1, mutant P53 and sIL-2R in HCC group. The results were discussed.
肝细胞癌(HCC)的发病率在全球范围内差异很大。慢性乙型肝炎病毒(HBV)感染和食品中黄曲霉毒素暴露是主要危险因素。P53基因第249密码子由精氨酸突变为丝氨酸(249ser)已被确定为一个热点,反映了黄曲霉毒素B1代谢产物在HCC中引起的DNA损伤。由于HBV感染在黄曲霉毒素高暴露地区往往呈地方性流行,目前尚不清楚HBV在249ser P53突变的发生发展中是作为混杂因素还是协同因素。血清可溶性白细胞介素2受体(sIL-2R)水平与肝硬化的进展相关,且与其病因无关。这一事实可能反映了肝硬化中T淋巴细胞、单核细胞和巨噬细胞的激活。本研究探讨了肝硬化和肝细胞癌患者中黄曲霉毒素暴露、HBV与HCV感染、P53与sIL-2R之间的相互关系。结果显示,与对照组相比,肝硬化患者和HCC患者血清中突变型P53、sIL-2R和黄曲霉毒素B1水平显著升高。HCC患者的所有三个参数水平均显著高于肝硬化患者和对照组(P<0.001)。在HCC组中发现血清黄曲霉毒素B1、突变型P53和sIL-2R之间存在相关性。对结果进行了讨论。