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


METHODS
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).


CONCLUSIONS
The UGT1A7 polymorphisms together with IL-1 beta were associated with the presence of HCC in Japanese HCV-infected patients.
Wang
Yue
Y
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Kato
Naoya
N
Hoshida
Yujin
Y
Otsuka
Motoyuki
M
Taniguchi
Hiroyoshi
H
Moriyama
Masaru
M
Shiina
Shuichiro
S
Kawabe
Takao
T
Ito
Yoichi M
YM
Omata
Masao
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics* / Q000821:virology; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006239:Haplotypes; D006526:Hepatitis C / Q000150:complications / Q000201:enzymology*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D007564:Japan; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors
D007375:Interleukin-1; D014453:Glucuronosyltransferase; C107611:UDP-glucuronosyltransferase, UGT1A7