Genetic polymorphism in the cytochrome P450-2C19 genes in Japanese patients with hepatocellu-lar carcinoma and hepatitis C infection

近年来，日本的肝细胞癌(肝细胞癌)人数有了显着的增加。肝细胞癌患者大多有丙型肝炎病毒相关的慢性肝炎和肝硬变。在日本，66%~94%的肝细胞癌患者抗-丙型肝炎病毒阳性而乙肝病毒表面(HBs)抗原阴性，而在美国，抗-丙型肝炎病毒阳性而乙肝病毒表面(HBs)抗原阴性的肝细胞癌患者中抗-HCV阳性而乙肝病毒表面(HBs)抗原阴性的患者占40%。这些结果表明物种差异(多态)的存在。由于环境致癌物部分影响肝细胞畸形的过程，包括致癌物在内的各种异源物质代谢能力的差异(日本人与高加索人)可能推断出两国之间肝细胞畸形频率的差异。我们利用基因分型方法对与P450亚型相关的药物代谢能力进行了分析，并将其分为广泛代谢物和较差代谢物。药理基因分型方法用聚合酶链式反应-限制性片段长度多态性方法筛选外显子4和外显子5，已被报道与药理表型有很好的一致性。我们对30例合并丙型肝炎病毒(+)的肝细胞癌患者进行了基因分型调查，发现30%的人在CYP2C19中存在低代谢者，70%的人在广泛代谢者中存在。肝癌的这一结果与健康日本人的结果基本相似，此外，此类患者的特征及其在广泛代谢物和不良代谢物之间的临床病程在临床环境中没有区别。

Recently there is a remarkable increase in population of hepatocellular carcinoma (HCC) in Japan. Most of the HCC patients have hepatitis C virus (HCV)-related chronic hepatitis and liver cirrhosis on their background disease condition. In Japan 66 to 94 percent in HCC patients are anti-HCV positive as well as negative hepatitis B virus surface (HBs) antigen, in contrast in United State there is markedly low frequency in HCC patients with positive anti-HCV and forty percent in HCC patients are anti-HCV positive and negative hepatitis B virus surface (HBs) antigen. These results indicate the presence of species difference (polymorphism). Since environmental carcinogen partly affect the process of hepatocyte malformation (HCC), the difference in metabolizing capability of various xenobitics including carcinogen (Japanese vs. Caucacian) may extrapolate such difference in HCC frequency between two countries. We analyzed and divided the drug metabolizing capability related P450 subtype CYP2C19 using genotyping into extensive and poor metabolizer. Pharmacogenotype method screening exon 4 and exon 5, using PCR-RFLP mehtod, has been reported to be well corresponding with pharmacological phenotype. Our genotype survey in 30 HCC patients with HCV(+) revealed 30% in poor metabolizer and 70% in extensive metabolizer in CYP2C19. This result in HCC was mostly similar to those in healthy Japanese, in addition such patients characteristics and their clinical course between extensive and poor metabolizer did not differ in clinical settings.