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J Hepatol. 2008 Nov;49(5):718-25. doi: 10.1016/j.jhep.2008.06.026. Epub 2008 Jul 24.

Sequential accumulation of the mutations in core promoter of hepatitis B virus is associated with the development of hepatocellular carcinoma in Qidong, China.

Author information

1
National Laboratory of Oncogene and Related Genes, Cancer Institute of Shanghai Jiao-Tong University, School of Medicine, Shanghai 200032, China.

Abstract

BACKGROUND/AIMS:

To investigate the mutations in hepatitis B virus (HBV) that might be related to hepatocellular carcinoma (HCC) in the high-risk area Qidong, China.

METHODS:

DNA sequences of HBV basal core promoter (BCP) and the overlapping X gene were determined in 58 HCC and 71 chronic hepatitis (CH) patients. In addition, a consecutive series of plasma samples from 15 HCC cases were employed to compare the CP/X sequences before and after the occurrence of HCC.

RESULTS:

T1762/A1764 double mutation was frequently found in Qidong patients, regardless of clinical status (65.5% in HCC and 73.2% in CH, P>0.05). Unexpectedly, the adjacent T1766/A1768 mutation significantly increased the risk of HCC (P<0.05). Moreover, the prevalence of triple mutations in BCP was significantly higher in patients with HCC than those with CH (P<0.05). The longitudinal study demonstrated that the mutations in BCP were gradually accumulated during the development of HCC. Colony formation assay showed while A1764 mutation alone did not alter the colony-inhibitory activity of HBx, double or triple mutations largely abrogated this effect.

CONCLUSIONS:

The complex mutation involving T1766/A1768 was closely related to HCC. The enhanced risk of HCC caused by BCP variants could be attributable partially to the aberrant activity of HBx.

PMID:
18801591
DOI:
10.1016/j.jhep.2008.06.026
[Indexed for MEDLINE]

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