Dataset Information

Relationship between the rs2596542 polymorphism in the MICA gene promoter and HBV/HCV infection-induced hepatocellular carcinoma: a meta-analysis.

ABSTRACT: BACKGROUND & AIMS:Various studies have investigated the relationship between the polymorphism, rs2596542, in the promoter of the major histocompatibility complex class I-related gene A (MICA) gene with susceptibility to hepatitis B virus (HBV)/ hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC); however, the results are inconclusive. This meta-analysis was conducted to investigate the relationship between rs2596542 and HCV/HBV-induced HCC. METHODS:Three electronic scientific publication databases (MEDLINE, Web of Science, and Embase) were screened using specific search terms and relevant literature identified using literature traceability methods. Selected publications were evaluated according to the inclusion and exclusion criteria, and 11 articles were included in the study. Effect size information (odds ratio [OR] and corresponding 95% confidence interval [CI]) were obtained following quality assessment and data extraction from the included publications, and a meta-analysis conducted. RESULTS:A total of 11 publications were included in the study, including 4582 patients with HCC and 21,095 non-HCC patients. TT genotype at rs2596542 was a risk factor for the development of HCC in patients with HCV/HBV infection (OR?=?1.248, 95% CI: 1.040-1.499, P?=?0.017), particularly those with HCV infection (OR?=?1.326, 95% CI: 1.101-1.599, P?=?0.003) and Asians (OR?=?1.273, 95% CI: 1.002-1.618, P?=?0.048), or when the control group was patients with chronic hepatitis C (CHC) (OR?=?1.506, 95% CI: 1.172-1.936, P?=?0.001). CONCLUSION:The findings of this meta-analysis suggest that the rs2596542 variant in the MICA promoter region may affect MICA and soluble MICA (sMICA) protein expression, thereby influencing physiological vulnerability to HCC cells and the development of HCC. These data provide a theoretical basis for the diagnosis and treatment of patients with HCC and viral hepatitis infection.

SUBMITTER: Luo X

PROVIDER: S-EPMC6697945 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Relationship between the rs2596542 polymorphism in the MICA gene promoter and HBV/HCV infection-induced hepatocellular carcinoma: a meta-analysis.

Luo Xiaojun X Wang Yu Y Shen Ai A Deng Hejun H Ye Min M

BMC medical genetics 20190816 1

<h4>Background & aims</h4>Various studies have investigated the relationship between the polymorphism, rs2596542, in the promoter of the major histocompatibility complex class I-related gene A (MICA) gene with susceptibility to hepatitis B virus (HBV)/ hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC); however, the results are inconclusive. This meta-analysis was conducted to investigate the relationship between rs2596542 and HCV/HBV-induced HCC.<h4>Methods</h4>Three electronic scie ...[more]

PMID: 31419949

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Project description:Background & aimsIn addition to HBV/HCV causing hepatocellular carcinoma (HCC), other risk factors including obesity and alcohol drinking also increase risk. We describe the cumulative risk of HCC and mortality from liver-related disease by selected modifiable risk factors among a non-hepatitis virus-infected population.MethodsFor a community-based cohort, residents aged 30-65 years living in 7 townships in Taiwan were recruited, and have been followed up since 1991. A total of 18,541 individuals were seronegative for markers of chronic infection of HBV/HCV and with no history of HCC at baseline. New non-HBV/HCV HCC cases and liver-related deaths were ascertained through data linkage to the National Cancer Registry and Death Certification System from 1 January 1991 through 31 December 2017.ResultsThere were 207 HCC cases and 215 liver-related deaths identified. The incidence rate of non-HBV/HCV HCC was 47.2 per 100,000 person-years. The mortality rate of liver-related death was 49.0 per 100,000 person-years. Baseline information on alcohol consumption, heart disease, diabetes, elevated aspartate aminotransferase, and alanine aminotransferase predicted higher risks of HCC, with hazard ratios (HRs) (95% CIs) of 1.7 (1.1-2.5), 2.2 (1.1-4.1), 1.9 (1.0-3.5), 1.7 (1.1-2.4), and 1.6 (1.0-2.4), respectively. The HRs (95% CIs) of liver-related death were 2.3 (1.6-3.2) for alcohol consumption, 1.4 (1.1-1.9) for BMI ≥25 kg/m2, 2.2 (1.4-3.3) for elevated aspartate aminotransferase, and 1.5 (1.0-2.4) for elevated alanine aminotransferase. The HR (95% CI) was 8.1 (3.6-18.5) for those with diabetes and elevated aspartate aminotransferase.ConclusionsIndividuals with elevated liver enzymes are at high risk of liver disease. Prevention and treatment of diabetes and heart disease are critical for non-hepatitis B, non-hepatitis C (NonB/C)-HCC.Lay summaryWe followed up individuals with no chronic HBV or HCV infection and described the risk of hepatocellular carcinoma (HCC, the most common form of primary liver cancer) and mortality from liver-related disease by modifiable risk factors. This study estimated the incidence rate of HCC by selected lifestyle risk factors and chronic diseases conditions. Alcohol consumption, heart disease, diabetes, and abnormal blood liver function tests showed a strong association with HCC risk and mortality.

Project description:MicroRNAs (miRNAs) exhibit essential regulatory functions related to cell growth, apoptosis, development and differentiation. Dysregulated expression of miRNAs is associated with a wide variety of human diseases. As such miRNA signatures are valuable as biomarkers for disease and for making treatment decisions. Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Here we screened for miRNAs in chronic HBV associated HCC.To determine the miRNAs in HCC occurrence associated with HBV infection, we analyzed global miRNA expression profiles in 12 pairs of HCC and adjacent matched non-HCC tissues from HBV-positive and HBV-negative patients using microarray analyses. The microarray result was validated by real-time PCR in 32 HBV-positive and 24 HBV-negative patient HCC samples. The potential candidate target genes of the miRNAs were predicted by miRWalk software. Genes simultaneously predicted as targets by two or more miRNAs were subjected to GO and KEGG pathway analysis. The miRNA regulatory network analysis was performed using the Ingenuity Pathway Analysis (IPA) software.Eight miRNAs (miR-223, miR-98, miR-15b, miR-199a-5p, miR-19b, miR-22, miR-451, and miR-101) were involved in HBV-unrelated HCC, 5 miRNAs (miR-98, miR-375, miR-335, miR-199a-5p, and miR-22) were involved in HBV infection, and 7 miRNAs (miR-150, miR-342-3p, miR-663, miR-20b, miR-92a-3p, miR-376c-3p and miR-92b) were specifically altered in HBV-related HCC. Gene Ontology and KEGG analyses predict that these HBV-related HCC miRNAs are involved in the regulation of: transcription, RNA polymerase II promoter, phosphorylation of proteins through MAPK signaling pathway, focal adhesion, and actin cytoskeleton. IPA analysis also suggest that these miRNAs act on AGO2, TP53, CCND1, and 11 other genes that significantly influence HCC occurrence and HBV infection.Our data indicates that the unique 7 miRNAs expression signature could be involved in the development HBV- related HCC.

Project description:Mechanisms of hepatic carcinogenesis in chronic hepatitis B and hepatitis C are incompletely defined but often assumed to be similar and related to immune-mediated inflammation. Despite this, several studies hint at differences in expression of miR-122, a liver-specific microRNA with tumor suppressor properties, in hepatocellular carcinoma (HCC) associated with hepatitis B virus (HBV) versus hepatitis C virus (HCV) infection. Differences in the expression of miR-122 in these cancers would be of interest, as miR-122 is an essential host factor for HCV but not HBV replication. To determine whether the abundance of miR-122 in cancer tissue is influenced by the nature of the underlying virus infection, we measured miR-122 by qRT-PCR in paired tumor and non-tumor tissues from cohorts of HBV- and HCV-infected Japanese patients. miR-122 abundance was significantly reduced from normal in HBV-associated HCC, but not in liver cancer associated with HCV infection. This difference was independent of the degree of differentiation of the liver cancer. Surprisingly, we also found significant differences in miR-122 expression in non-tumor tissue, with miR-122 abundance reduced from normal in HCV- but not HBV-infected liver. Similar differences were observed in HCV- vs. HBV-infected chimpanzees. Among HCV-infected Japanese subjects, reductions in miR-122 abundance in non-tumor tissue were associated with a single nucleotide polymorphism near the IL28B gene that predicts poor response to interferon-based therapy (TG vs. TT genotype at rs8099917), and correlated negatively with the abundance of multiple interferon-stimulated gene transcripts. Reduced levels of miR-122 in chronic hepatitis C thus appear to be associated with endogenous interferon responses to the virus, while differences in miR-122 expression in HCV- versus HBV-associated HCC likely reflect virus-specific mechanisms contributing to carcinogenesis. The continued expression of miR-122 in HCV-associated HCC may signify an important role for HCV replication late in the progression to malignancy.

Dataset Information

Relationship between the rs2596542 polymorphism in the MICA gene promoter and HBV/HCV infection-induced hepatocellular carcinoma: a meta-analysis.

Publications

Relationship between the rs2596542 polymorphism in the MICA gene promoter and HBV/HCV infection-induced hepatocellular carcinoma: a meta-analysis.

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