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

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, P A=0.0007; CC + CT vs. TT: OR = 1.38, 95% CI: 1.09-1.76, P A=0.008). Validation with all the genetic models revealed that rs7574865 polymorphism of STAT4 gene was closely associated with chronic HBV infection (P A<0.01) and chronic hepatitis B (CHB)-related HCC (P A<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.

SUBMITTER: Shi H

PROVIDER: S-EPMC6616055 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Shi Han H He Hongyan H Ojha Suvash Chandra SC Sun Changfeng C Fu Juan J Yan Mao M Deng Cunliang C Sheng Yunjian Y

Bioscience reports 20190620 6

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 o ...[more]

PMID: 31160486

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Project description:BackgroundHepatocellular carcinoma (HCC) is an intractable public health threat worldwide, representing the second leading cause of cancer-related mortality, with limited early detection and therapeutic options. Recent findings have revealed that the susceptibility of HCC is closely related to microRNA (miRNA). We performed this systematic review with a network meta-analysis to investigated four single nucleotide polymorphisms (SNPs) that most regularly reported in miRNAs, exploring their involvement in HCC susceptibility and interaction with hepatitis B virus (HBV).MethodsDatabases were reviewed for related studies published up to May 2019 to identify all studies that compared genotypes of miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913, and miR-499 rs3746444 with no language and date restrictions. A pairwise meta-analysis was performed to estimate pooled odds ratios and 95% confidence intervals incorporating heterogeneity to assess the relationship between four miRNA polymorphisms and HCC. To further clarify the effect of polymorphisms on HCC, a Bayesian network meta-analysis was conducted to combine the effective sizes of direct and indirect comparisons. Calculations were performed by R version 3.6.1 and STATA 14.0. All steps were performed according to PRISMA guidelines.ResultsA total of 20 studies were enrolled in this network meta-analysis, providing 5,337 hepatocellular carcinoma cases and 6,585 controls. All included studies had an acceptable quality. Pairwise meta-analysis demonstrated that miR-196a2 rs11614913 was significantly associated with the susceptibility of HCC, while the other three SNPs were not found to have a significant association. In the analysis of HCC patients under different HBV infection status, only miR-196a2 revealed correlation of threefold risk. The network results showed no significant difference in the distribution of genotype frequencies except for miR-196a2, which appeared to have the highest superiority index when comparing and ranking four SNPs.ConclusionMiR-196a2 rs11614913 was significantly associated with the susceptibility of HCC, especially for HBV- related HCC, and that individuals with TC/CC were more susceptible. No significant association was found in the other three miRNA genes. MiR-196a2 could serve as the best predictor of susceptibility in HCC.

Dataset Information

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

Publications

Association of <i>STAT3</i> and <i>STAT4</i> polymorphisms with susceptibility to chronic hepatitis B virus infection and risk of hepatocellular carcinoma: a meta-analysis.

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