scholarly journals Genome-wide association study of TP53 R249S mutation in hepatocellular carcinoma with aflatoxin B1 exposure and hepatitis B virus infection in Guangxi

2020 ◽  
Author(s):  
Chuangye Han ◽  
Tingdong Yu ◽  
Wei Qin ◽  
Xiwen Liao ◽  
Jianlu Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Tumor Tissue ◽  
Genome Wide Association Study ◽  
Hbv Infection ◽  
Genome Wide Association ◽  
Chronic Hbv Infection ◽  
Genome Wide ◽  
B Virus ◽  
Chronic Hbv

AbstractBackground/AimsDietary aflatoxin B1 (AFB1) exposure, which induces DNA damage and codon 249 mutation of the TP53 gene, is one of the major risk factors for hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) infection and AFB1 exert synergistic effects to promote carcinogenesis and TP53 R249S mutation in HCC.MethodsA genome-wide association study (GWAS) was conducted on 485 cases of HCC with chronic HBV infection, followed by a two-stage replication study on 270 cases with chronic HBV infection. Susceptibility variants for the TP53 R249S mutation in HCC were identified based on both GWAS and replication analysis. The associations of identified variants with expression levels of their located genes were validated in 20 paired independent samples.ResultsOur results showed that TP53 R249S was significantly associated with ADAMTS18 rs9930984 (adjusted P = 4.84×10−6), WDR49 rs75218075 (adjusted P = 7.36 × 10−5) and SLC8A3 rs8022091 (adjusted P = 0.042). Additionally, ADAMTS18 mRNA expression was significantly higher in HCC tissue, compared with paired non-tumor tissue (P = 0.041) and patients carrying the TT genotype at rs9930984 showed lower ADAMTS18 expression in non-tumor tissue, compared with those carrying the GT genotype (P = 0.0028).ConclusionsTP53 expression is significantly associated with R249S mutation in HCC. Our collective results suggest that rs9930984, rs75218075 and rs8022091 are associated with susceptibility to the R249S mutation in cases of HCC exposed to AFB1 and HBV infection.

scholarly journals Association of STAT3 and STAT4 polymorphisms with susceptibility to chronic hepatitis B virus infection and risk of hepatocellular carcinoma: a meta-analysis

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Han Shi ◽  
Hongyan He ◽  
Suvash Chandra Ojha ◽  
Changfeng Sun ◽  
Juan Fu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Meta Analysis ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
B Virus ◽  
Chronic Hbv

Abstract Background: It has been reported that polymorphisms of signal transducer and activator of transcription (STAT) 3 and STAT4 might be associated with susceptibility to hepatitis B virus (HBV) infection and risk of chronic hepatocellular carcinoma (HCC). Owing to limitation of sample size and inconclusive results, we conducted a meta-analysis to clarify the association. Methods: We identified relevant studies by a systematic search of Medline/PubMed, Embase, Web of Science and the Cochrane Library up to 20 February 2019. The strength of the association measured by odds ratios (OR) with 95% confidence intervals (CIs) was studied. All the statistical analyses were conducted based on Review Manager 5.3 software. Results: A total of 5242 cases and 2717 controls from five studies were included for the STAT3 polymorphism, 5902 cases and 7867 controls from nine studies for the STAT4 polymorphism. Our results suggested that STAT3 rs1053004 polymorphism was a significant risk factor of chronic HBV infection (C vs. T: OR = 1.17, 95% CI: 1.07–1.29, PA=0.0007; CC + CT vs. TT: OR = 1.38, 95% CI: 1.09–1.76, PA=0.008). Validation with all the genetic models revealed that rs7574865 polymorphism of STAT4 gene was closely associated with chronic HBV infection (PA<0.01) and chronic hepatitis B (CHB)-related HCC (PA<0.05). Meanwhile, the authenticity of the above meta-analysis results was confirmed by trial sequential analysis (TSA). Conclusions: The meta-analysis showed that STAT3 rs1053004 polymorphism may be the risk for developing chronic HBV infection but not associated with HCC. The present study also indicates that STAT4 rs7574865 polymorphism increased the risk of chronic HBV infection and HCC.

scholarly journals Impact of Hepatitis B Virus (HBV) X Gene Mutations on Hepatocellular Carcinoma Development in Chronic HBV Infection

2013 ◽  
Vol 20 (1) ◽  
pp. 127-127 ◽  
Author(s):  
Jong-Han Lee ◽  
Kwang-Hyub Han ◽  
Jae Myun Lee ◽  
Jeon Han Park ◽  
Hyon-Suk Kim
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Gene Mutations ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
B Virus ◽  
Chronic Hbv ◽  
X Gene

Hepatitis B Virus

2021 ◽  
Author(s):  
Ming V. Lin ◽  
April Wall
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Infection ◽  
Treatment Options ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Chronic Hbv

Chronic hepatitis B virus (HBV) infection is a major health burden worldwide, with approximately 257 million people with chronic infection. HBV is a small partially double-stranded DNA virus that replicates within the nucleus of the hepatocyte and commonly leads to chronic infection. Chronic HBV infection can cause cirrhosis, hepatocellular carcinoma, and extrahepatic manifestations such as glomerulonephritis or vasculitis. The latter is due to deposition of circulating immune complex in the different tissues. The natural history of HBV infection can be conceptualized as a spectrum encompassing different phases, including immune tolerance, immune clearance, inactive carrier, and reactivation and resolution. The diagnosis of the different phases of chronic HBV infection relies on various HBV serologies, liver enzyme levels, and histology findings. There are currently eight therapies approved for the treatment of HBV. Tenofovir alafenamide was the most recently approved therapy with a better side effect profile compared with tenofovir disoproxil fumarate. With the recent advances in the basic research in hepatitis B, new treatment options may become available in the near-future. This review contains 9 figures, 11 tables and 80 references Key words: cirrhosis, entecavir, Hepadnaviridae, hepatitis B virus, hepatocellular carcinoma, precore mutation, tenofovir

Hepatitis B Virus

2021 ◽  
Author(s):  
Ming V. Lin ◽  
April Wall
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Infection ◽  
Treatment Options ◽  
Hbv Infection ◽  
Chronic Hbv Infection ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Chronic Hbv

Chronic hepatitis B virus (HBV) infection is a major health burden worldwide, with approximately 257 million people with chronic infection. HBV is a small partially double-stranded DNA virus that replicates within the nucleus of the hepatocyte and commonly leads to chronic infection. Chronic HBV infection can cause cirrhosis, hepatocellular carcinoma, and extrahepatic manifestations such as glomerulonephritis or vasculitis. The latter is due to deposition of circulating immune complex in the different tissues. The natural history of HBV infection can be conceptualized as a spectrum encompassing different phases, including immune tolerance, immune clearance, inactive carrier, and reactivation and resolution. The diagnosis of the different phases of chronic HBV infection relies on various HBV serologies, liver enzyme levels, and histology findings. There are currently eight therapies approved for the treatment of HBV. Tenofovir alafenamide was the most recently approved therapy with a better side effect profile compared with tenofovir disoproxil fumarate. With the recent advances in the basic research in hepatitis B, new treatment options may become available in the near-future. This review contains 9 figures, 11 tables and 80 references Key words: cirrhosis, entecavir, Hepadnaviridae, hepatitis B virus, hepatocellular carcinoma, precore mutation, tenofovir

scholarly journals Impact of Hepatitis B Virus (HBV) X Gene Mutations on Hepatocellular Carcinoma Development in Chronic HBV Infection

2011 ◽  
Vol 18 (6) ◽  
pp. 914-921 ◽  
Author(s):  
Jong-Han Lee ◽  
Kwang-Hyub Han ◽  
Jae Myun Lee ◽  
Jeon Han Park ◽  
Hyon-Suk Kim
Keyword(s):  
Hepatocellular Carcinoma ◽  
Risk Factor ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Infection ◽  
Regulatory Pathways ◽  
Chronic Hbv Infection ◽  
B Virus ◽  
Chronic Hbv ◽  
The Impact

ABSTRACTThe hepatitis B virus (HBV) PreS mutations C1653T, T1753V, and A1762T/G1764A were reported as a strong risk factor of hepatocellular carcinoma (HCC) in a meta-analysis. HBV core promoter overlaps partially with HBx coding sequence, so the nucleotide 1762 and 1764 mutations induce HBV X protein (HBx) 130 and 131 substitutions. We sought to elucidate the impact of HBx mutations on HCC development. Chronically HBV-infected patients were enrolled in this study: 42 chronic hepatitis B (CHB) patients, 23 liver cirrhosis (LC) patients, and 31 HCC patients. Direct sequencing showed HBx131, HBx130, HBx5, HBx94, and HBx38 amino acid mutations were common in HCC patients. Of various mutations, HBx130+HBx131 (double) mutations and HBx5+HBx130+HBx131 (triple) mutations were significantly high in HCC patients. Double and triple mutations increased the risk for HCC by 3.75-fold (95% confidence interval [CI] = 1.101 to 12.768,P= 0.033) and 5.34-fold (95% CI = 1.65 to 17.309,P= 0.005), respectively, when HCC patients were compared to CHB patients. Functionally, there were significantly higher levels of NF-κB activity in cells with the HBx5 mutant and with the double mutants than that of wild-type cells and the triple-mutant cells. The triple mutation did not increase NF-κB activity. Other regulatory pathways seem to exist for NF-κB activation. In conclusion, a specific HBx mutation may contribute to HCC development by activating NF-κB activity. The HBx5 mutation in genotype C2 HBV appears to be a risk factor for the development of HCC and may be used to predict the clinical outcomes of patients with chronic HBV infection.

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