A case–control study on sequence variations in the enhancer II/core promoter/precore and X genes of hepatitis B virus in patients with hepatocellular carcinoma

Tangkijvanich, Pisit; Sa-nguanmoo, Pattaratida; Mahachai, Varocha; Theamboonlers, Apiradee; Poovorawan, Yong

doi:10.1007/s12072-010-9197-z

Cited by 24 publications

(23 citation statements)

References 34 publications

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“…Therefore, it is not surprising that T1753V is more frequently linked to HBV genotype C than genotype B (19.2% vs 1.9%; P = 0.013) [15] . G1899A combined with the BCP double mutation is the single risk factor indicating HCC risk in Thailand and Tunisia, but the linkages between mutations are less clear in South Korea [33,37,45,48] . Our data indicate that while G1896A increases steadily with time, the accumulation of A1846T begins to increase during the quadruple phase of mutations.…”

Section: Mutationmentioning

confidence: 98%

“…These effects can subsequently modulate the immune response to viral antigens and enhance the carcinogenic effects of altered X proteins [40] . In Far East Asia, HBV genotypes B and C are predominant, and five mutations are prominent in the core promoter and proximal precore regions: G1613A, C1653T, T1753V, A1846T, and G1899A [43][44][45][46][47] . These select mutations are associated with the development of HCC when combined with the BCP double mutation.…”

Section: Key Mutations In the Core Promoter And Proximal Precore Regimentioning

confidence: 99%

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Clinical utility of complex mutations in the core promoter and proximal precore regions of the hepatitis B virus genome

Park¹

2015

WJH

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The core promoter and proximal precore regions are the most complex portions of the hepatitis B virus (HBV) genome. These regions cooperatively regulate viral replication and differentially regulate the synthesis of the viral proteins E, core, and X. Multiple mutations in these regions are associated with the persistency of viral infection and the development of cirrhosis and hepatocellular carcinoma (HCC). In South Korea, nearly all HBVs are classified as HBV genotype C2; the majority of these viruses have the basal core promoter double mutation, a precore stop mutation, or both. These mutations may play a role in the alteration of viral and clinical features, and abundant and complex mutations are particularly prevalent in the core promoter and proximal precore regions. We previously demonstrated that the accumulation of ≥ 6 mutations at eight key nucleotides located in these regions (G1613A, C1653T, T1753V, A1762T, G1764A, A1846T, G1896A, and G1899A) is a useful marker to predict the development of HCC regardless of advanced liver disease. In addition, certain mutation combinations were predominant in cases with ≥ 4 mutations. In cases with ≤ 5 mutations, a low Hepatitis B e antigen titer (< 35 signal to noise ratio) was indicative of HCC risk. Viral mutation data of the single HBV genotype C2 suggest that the combined effect of the number and pattern of mutations in the core promoter and proximal precore regions is helpful in predicting HCC risk.

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Section: Mutationmentioning

confidence: 98%

Section: Key Mutations In the Core Promoter And Proximal Precore Regimentioning

confidence: 99%

Clinical utility of complex mutations in the core promoter and proximal precore regions of the hepatitis B virus genome

Park¹

2015

WJH

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“…These studies included 1 study in Chinese and 10 in English (6,11,13,(16)(17)(18)(19)(20)(21)(22)(23). A detailed flow chart explaining the inclusion of studies is shown in Fig.…”

Section: Study Characteristicsmentioning

confidence: 99%

HBV X gene point mutations are associated with the risk of hepatocellular carcinoma: A systematic review and meta-analysis

Wang

Zeng

Chen

2016

Molecular and Clinical Oncology

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Abstract. Previous evidence suggests that the accumulation of the hepatitis B virus (HBV) X gene region point mutations may be associated with the development of hepatocellular carcinoma (HCC). However, the pathogenesis of HCC remains to be elucidated. The aim of the present meta-analysis was to investigate the association between the HBV X gene point mutations and the risk of HCC. Studies were collected regarding the association between HBV X gene point mutations and the risk of HCC, which were identified in PubMed, EMBASE and China National Knowledge Infrastructure databases. The results were evaluated by use of odds ratios (ORs) and its 95% confidence intervals (CIs), which were pooled by random or fixed effects. A total of 11 studies involving 2,502 patients were included in this meta-analysis. Statistical summary ORs of HBV X gene point mutations were obtained for T1653 (OR, 3.11; 95% CI, 2.22-4.36), V1753 (OR, 2.55; 95% CI, 1.66-3.92), and T1762/A1764 (OR, 4.49; 95% CI, 2.86-7.07). HBV X gene point mutations T1653, V1753 and T1762/A1764 could increase the risk of HCC significantly, particularly the T1762/A1764 double mutations. These mutations may be predictive for hepatocarcinogenesis. However, these results of the meta-analysis should be treated carefully due to a low level of evidence.

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“…Also, preSl and preS2 promoter mutations have been reported to be significandy higher in HCC patients (19.7 vs 3% and 15.3 vs 8.9%, respectively) [142]. Additionally, a precore mutation, G1899A, has been found to be significantly associated with HCC in Thailand [160,161]. …”

Section: Hbv-based Viral Dna Markersmentioning

confidence: 99%

DNA markers in molecular diagnostics for hepatocellular carcinoma

Lin

Song

et al. 2014

Expert Review of Molecular Diagnostics

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Hepatocellular carcinoma (HCC) is the one of the leading causes of cancer mortality in the world, mainly due to the difficulty of early detection and limited therapeutic options. The implementation of HCC surveillance programs in well-defined, high-risk populations were only able to detect about 40–50% of HCC at curative stages (Barcelona Clinic Liver Cancer stages 0 & 1) due to the low sensitivities of the current screening methods. The advance of sequencing technologies has identified numerous modifications as potential candidate DNA markers for diagnosis/surveillance. Here we aim to provide an overview of the DNA alterations that result in activation of cancer pathways known to potentially drive HCC carcinogenesis and to summarize performance characteristics of each DNA marker in the periphery (blood or urine) for HCC screening.

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A case–control study on sequence variations in the enhancer II/core promoter/precore and X genes of hepatitis B virus in patients with hepatocellular carcinoma

Cited by 24 publications

References 34 publications

Clinical utility of complex mutations in the core promoter and proximal precore regions of the hepatitis B virus genome

Clinical utility of complex mutations in the core promoter and proximal precore regions of the hepatitis B virus genome

HBV X gene point mutations are associated with the risk of hepatocellular carcinoma: A systematic review and meta-analysis

DNA markers in molecular diagnostics for hepatocellular carcinoma

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