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UDP-Glucuronosyltransferase 1A7 Genetic Polymorphisms Are Associated with Hepatocellular Carcinoma in Japanese Patients with Hepatitis C Virus Infection

¹ Department of Gastroenterology, Graduate School of Medicine, and ² Interfaculty Initiative in Information Studies, Graduate School of Interdisciplinary Information Studies, Department of Biostatistics/Epidemiology and Preventive Health Sciences, School of Health Sciences and Nursing, University of Tokyo, Tokyo, Japan

Purpose: 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-1ß (IL-1ß) 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.

Experimental Design: Genetic polymorphisms of UGT1A7 and IL-1ß 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.

Results: 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-1ß/–31T/T–511C/C genotypes, the presence of cirrhosis, age >60 years, male sex, and -fetoprotein >20 µg/ml were associated with the presence of HCC (odds ratios, 2.33, 2.67, 4.20, 3.12, 3.09, and 2.90, respectively).

Conclusion: The UGT1A7 polymorphisms together with IL-1ß were associated with the presence of HCC in Japanese HCV-infected patients.

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