Lee H S, Yoon J H, Kamimura S, Iwata K, Watanabe H, Kim C Y
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Korea.
Int J Cancer. 1997 May 29;71(5):737-40. doi: 10.1002/(sici)1097-0215(19970529)71:5<737::aid-ijc8>3.0.co;2-s.
The iso-enzyme pattern of cytochrome P450 was shown to be related to the development of chemically induced hepatocellular carcinoma (HCC) in rats, which is accelerated by chronic alcohol ingestion. Our study was designed to investigate the association of cytochrome P450 2E1 (CYP2E1) genetic polymorphisms with the susceptibility to HCC in humans with and without chronic alcohol ingestion. We enrolled 171 male patients (108 Korean and 63 Japanese) with HCC and 31 age- and sex-matched healthy Korean subjects with no evidence of liver disease or cancer in any organ. Genotypes in the 5'-flanking region of the CYP2E1 gene were determined by restriction fragment length polymorphisms using 2 endonucleases: Pst I and Rsa I. Allelic frequencies in the CYP2E1 5'-flanking region in the Korean control population were 83.5% and 16.5% for allele c1 and c2, respectively. The frequencies of genotypes with the c2 allele (c1/c2 and c2/c2) were compared with those of genotypes without c2 (c1/c1) among HCC patients and controls, according to the pattern of alcohol consumption. There was no significant association between HCC risk and genotypes c1/c2 and c2/c2 either in all HCC patients or in HCC patients of different ethnic groups. Habitual drinkers with HCC, especially among Koreans, were more likely to carry genotype c1/c2 and c2/c2 (odds ratio = 3.0) than non-habitual drinkers (odds ratio = 1.2); however, the difference was not statistically significant. Even when patients were restricted to those without hepatitis B surface antigen and antibodies against hepatitis C virus but with a history of chronic alcohol ingestion, there was still no increased risk of HCC in those with genotypes c1/c2 and c2/c2. We conclude that there is a lack of association of the polymorphisms of CYP2E1 with the risk of HCC in humans.
细胞色素P450的同工酶模式被证明与大鼠化学诱导的肝细胞癌（HCC）的发生有关，慢性酒精摄入会加速这种癌症的发展。我们的研究旨在调查细胞色素P450 2E1（CYP2E1）基因多态性与有无慢性酒精摄入的人类患HCC易感性之间的关联。我们招募了171名男性HCC患者（108名韩国人和63名日本人）以及31名年龄和性别匹配的健康韩国受试者，这些受试者没有任何器官的肝病或癌症迹象。使用两种核酸内切酶Pst I和Rsa I，通过限制性片段长度多态性确定CYP2E1基因5'侧翼区域的基因型。在韩国对照人群中，CYP2E1 5'侧翼区域的等位基因c1和c2的频率分别为83.5%和16.5%。根据饮酒模式，比较了HCC患者和对照组中带有c2等位基因的基因型（c1/c2和c2/c2）与不带有c2的基因型（c1/c1）的频率。在所有HCC患者或不同种族的HCC患者中，HCC风险与基因型c1/c2和c2/c2之间均无显著关联。患有HCC的习惯性饮酒者，尤其是韩国人，比非习惯性饮酒者更有可能携带基因型c1/c2和c2/c2（优势比 = 3.0）；然而，差异无统计学意义。即使将患者限制为那些没有乙肝表面抗原和抗丙肝病毒抗体但有慢性酒精摄入史的人，基因型为c1/c2和c2/c2的人患HCC的风险仍然没有增加。我们得出结论，CYP2E1多态性与人类患HCC的风险之间缺乏关联。
