Wang Yue, Kato Naoya, Hoshida Yujin, Otsuka Motoyuki, Taniguchi Hiroyoshi, Moriyama Masaru, Shiina Shuichiro, Kawabe Takao, Ito Yoichi M, Omata Masao
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Clin Cancer Res. 2004 Apr 1;10(7):2441-6. doi: 10.1158/1078-0432.ccr-1187-3.
Genetic polymorphisms of UDP-glucuronosyltransferase 1A7 (UGT1A7), which detoxifies endogenous and environmental carcinogens, have been reported to be associated with hepatocellular carcinoma (HCC) in German populations. On the other hand, we reported that interleukin-1 beta (IL-1 beta) gene polymorphisms were associated with hepatitis C virus (HCV)-related HCC. In this study, we evaluated the association of both genes with the risk of HCC in Japanese HCV-infected patients.
Genetic polymorphisms of UGT1A7 and IL-1 beta were investigated in 280 Japanese patients (122 with HCC and 158 without HCC) with chronic HCV infections, by use of standard PCR-based genotyping techniques.
We designated the UGT1A7*1 allele (a haplotype conferring higher activity) as H and the *2, *3, and *4 alleles (haplotypes conferring lower activity) as L. The proportions of UGT1A7 L/L and H/L alleles (genotypes) in patients with HCC (25% and 45%, respectively) were higher than those in patients without HCC (15% and 39%, respectively) with odds ratios of 2.73 (95% confidence interval, 1.40-5.35) and 1.80 (95% confidence interval, 1.05-3.09), respectively, compared with the UGT1A7 H/H alleles. Multivariate analyses revealed that UGT1A7 L/L and IL-1 beta/-31T/T-511C/C genotypes, the presence of cirrhosis, age >60 years, male sex, and alpha-fetoprotein >20 microg/ml were associated with the presence of HCC (odds ratios, 2.33, 2.67, 4.20, 3.12, 3.09, and 2.90, respectively).
The UGT1A7 polymorphisms together with IL-1 beta were associated with the presence of HCC in Japanese HCV-infected patients.
尿苷二磷酸葡萄糖醛酸基转移酶1A7（UGT1A7）可使内源性和环境致癌物解毒，据报道其基因多态性与德国人群的肝细胞癌（HCC）相关。另一方面，我们报道白细胞介素-1β（IL-1β）基因多态性与丙型肝炎病毒（HCV）相关的HCC有关。在本研究中，我们评估了这两个基因与日本HCV感染患者发生HCC风险的相关性。
采用基于标准PCR的基因分型技术，对280例慢性HCV感染的日本患者（122例HCC患者和158例非HCC患者）的UGT1A7和IL-1β基因多态性进行了研究。
我们将UGT1A71等位基因（一种具有较高活性的单倍型）指定为H，将2、3和4等位基因（具有较低活性的单倍型）指定为L。HCC患者中UGT1A7 L/L和H/L等位基因（基因型）的比例（分别为25%和45%）高于非HCC患者（分别为15%和39%），与UGT1A7 H/H等位基因相比，优势比分别为2.73（95%置信区间，1.40 - 5.35）和1.80（95%置信区间，1.05 - 3.09）。多因素分析显示，UGT1A7 L/L和IL-1β/-31T/T - 511C/C基因型、肝硬化的存在、年龄>60岁、男性以及甲胎蛋白>20μg/ml与HCC的存在相关（优势比分别为2.33、2.67、4.20、3.12、3.09和2.90）。
在日本HCV感染患者中，UGT1A7多态性与IL-1β共同与HCC的存在相关。
