Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Wang, Y. et al.

UDP-glucuronosyltransferase 1A7 genetic polymorphisms are associated with hepatocellular carcinoma in japanese patients with hepatitis C virus infection.

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-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. EXPERIMENTAL DESIGN: 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. 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-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). CONCLUSION: The UGT1A7 polymorphisms together with IL-1 beta were associated with the presence of HCC in Japanese HCV-infected patients.[1]

References

UDP-glucuronosyltransferase 1A7 genetic polymorphisms are associated with hepatocellular carcinoma in japanese patients with hepatitis C virus infection. Wang, Y., Kato, N., Hoshida, Y., Otsuka, M., Taniguchi, H., Moriyama, M., Shiina, S., Kawabe, T., Ito, Y.M., Omata, M. Clin. Cancer Res. (2004) [Pubmed]

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