Hepatitis B virus core promoter mutations G1613A and C1653T are significantly associated with hepatocellular carcinoma in genotype C HBV-infected patients

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Hepatitis B virus core promoter mutations G1613A and C1653T are significantly

associated with hepatocellular carcinoma in genotype C HBV-infected patients

Hepatitis B virus (HBV) is a major cause of hepatocarcinogenesis.To identify

mutations relevant to hepatocellular carcinoma (HCC) development, we compared

the full genome sequences of HBV from the sera of patients with and without HCC.

Methods: We compared the full genome sequences of HBV isolates from 37 HCC

patients (HCC group 1) and 38 patients without HCC (non-HCC group 1).

We also investigated part of the core promoter region sequences from 40 HCC

patients (HCC group 2) and 68 patients without HCC. Of the 68 patients who

initially did not have HCC, 52 patients remained HCC-free during the follow-up

period (non-HCC group 2), and 16 patients eventually developed HCC (pre-HCC

group 2).

Serum samples collected from patients were subjected to PCR, and the HBV DNA was

directly sequenced.

Results: All patients had genotype C.

A comparison of the nucleotide sequences of the HBV genome between HCC group 1

and non-HCC group 1 revealed that the prevalence of G1613A and C1653T mutations

in the core promoter region was significantly higher in the HCC group. These

mutations tended to occur simultaneously in HCC patients.

Multivariate analysis with group 2 revealed that the presence of HCC was

associated with aging and the double mutation. Future emergence of HCC was

associated with aging and the presence of a single G1613A mutation.

Conclusions: G1613A and C1653T double mutations were frequently found in

patients with HCC. A single G1613A mutation was associated with future emergence

of HCC.

These mutations may serve as useful markers in predicting HCC development.

Author: Masashi TatsukawaAkinobu TakakiHidenori ShirahaKazuko KoikeYoshiaki

IwasakiHaruhiko KobashiShin-ichi FujiokaKohsaku SakaguchiKazuhide Yamamoto

Credits/Source: BMC Cancer 2011, 11:458