Nucleotide changes related to hepatocellular carcinoma in the enhancer 1/x-promoter of hepatitis B virus subgenotype C2 in cirrhotic patients.

Abstract

Hepatocellular carcinoma (HCC) is widely known to develop more frequently in cirrhotic patients with a high expression of Hepatitis B virus X protein (HBx), which is controlled by the enhancer 1 (Enh1)/X-promoter. To examine the effect of the mutations in the Enh1/X-promoter region in hepatitis B virus (HBV) genomes on the development of HCC, we investigated the differences in HBV isolated from cirrhotic patients with or without HCC along with the promoter activities of certain specific mutations within the Enh1/X-promoter. We examined 160 hepatitis B surface antigen (HBsAg)-positive cirrhotic patients (80 HCC patients, 80 non-HCC patients) by evaluating the biochemical, virological, and molecular characteristics. We evaluated the functional differences in certain specific mutations within the Enh1/X-promoter. The isolated sequences included all of the subgenotypes C2. The sites that showed higher mutation rates in the HCC group were G1053A and G1229A, which were found to be independent risk factors through multiple logistic analysis (P < 0.05). Their promoter activities were elevated 2.38- and 4.68-fold, respectively, over that of the wild type in the HepG2 cells. Similarly, both the mRNA and protein levels of HBx in these two mutants were much higher than that in wild type-transfected HepG2 cells. Mutated nucleotides of the Enh1/X-promoter, especially G1053A and G1229A mutations in the HBV subgenotype C2 of patients with cirrhosis, can be risk factors for hepatocarcinogenesis, and this might be due to an increase in the HBx levels through the transactivation of the Enh1/X-promoter.

DOI: 10.1111/j.1349-7006.2010.01612.x

Cite this paper

@article{Cho2010NucleotideCR, title={Nucleotide changes related to hepatocellular carcinoma in the enhancer 1/x-promoter of hepatitis B virus subgenotype C2 in cirrhotic patients.}, author={Eun-Young Cho and Haak-Cheoul Kim and Chang-Soo Choi and Sae Ron Shin and Channy Park and Hong-Seob So and Hyung Jin Kim and Raekil Park and Ji Hyun Cho and Hyung Bae Moon}, journal={Cancer science}, year={2010}, volume={101 8}, pages={1905-12} }