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

Abstract

BackgroundHepatitis 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.MethodsWe 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.ResultsAll 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.ConclusionsG1613A 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.

Hepatitis B Virus Gene Mutations and Hepatocarcinogenesis

“…is also associated with HCC in patients infected with HBV genotype C (Mun et al, 2011). On the other hand, some studies have detected that the pre-S internal deletion mutants are unlikely to play an important role in hepatocarcinogenesis in clinical study (Tatsukawa et al, 2011). Numerous studies for mechanisms shown that deletions mutations in Pre-S in the integrated HBV DNA, may impair the secretion of HBsAg, leading to increased endoplasmic reticulum and oxidative stress in hepatocytes .…”

Genetic Factors, Viral Infection, Other Factors and Liver Cancer: An Update on Current Progress

“…Mutations in basal core promoter may also involved in the development of carcinoma, the result of direct sequencing revealed that mutations including A1896, A1899 and multiple mutations T1762/A1764+A1896, T1762/A1764+A1899, and T1762/A1764+A1896+A1899 were more common in cirrhotic hepatocellular carcinoma group and non-cirrhotic hepatocellular carcinoma than chronic hepatitis B patients (Zheng et al, 2011). Moreover, a study with 37 patients and 38 controls has been performed and reported G1613A and C1653T double mutations were more prevalent in patients with HCC, thus, those mutations may serve as makers in predicting HCC development (Tatsukawa et al, 2011). Being compared with both carriers of inactive virus (25%) or patients with chronic hepatitis(35%), the frequency of T1653 mutation in box alpha, the rate among patients with HCC (70%) was significantly higher, suggesting it would lead to elevated risk of HCC (Ito et al, 2006).…”

Hepatitis B Virus Gene C1653T Polymorphism Mutation and Hepatocellular Carcinoma Risk: an Updated Meta-analysis

“…Base on the inclusion criteria, only 17 case-control studies (Sakamoto et al, 2006;Tanaka et al, 2006;Shinkai et al, 2007;Wang et al, 2007;Yuan et al, 2007;Zhang et al, 2007;Fang et al, 2008;Guo et al, 2008;Jang et al, 2008;Choi et al, 2009;Ja et al, 2009;Tangkijvanich et al, 2010;Welschinger et al, 2010;Zhu et al, 2010;Cho et al, 2011;Qu et al, 2011;Tatsukawa et al, 2011) with full-text were included in this meta-analysis and 18 studies were excluded. The flow chart of study selection is summarized in Figure 1.…”