Skip to main content
SpringerLink
Log in

STAT4 Gene Polymorphism and Risk of Chronic Hepatitis B-Induced Hepatocellular Carcinoma

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

STAT4 is a latent cytosolic factor that encodes a transcription factor transmitting signals stimulated by cytokines. Previous studies with different study designs in diverse ethnic populations have assessed the influence of STAT4 rs7574865 polymorphism on HBV-induced HCC risk. The aim of the current study was to investigate the effects in a larger sample. The individual reports published up to Dec. 30, 2013 were systematically identified by searching the PubMed and Embase databases. To combine the OR and corresponding 95 % CI, we used the fixed effects model during meta-analysis. Based on eight independent populations with a total of 5,719 cases and 6,525 controls, we found a slightly reduced risk of HBV-induced HCC in individuals with the minor T allele compared with individuals with the common G allele (T versus G: OR = 0.87, 95 % CI = 0.82–0.91, PHet = 0.974). Similar reductions were also indicated in all subgroups. The combined data indicate that STAT4 rs7574865 polymorphism may be associated with significantly reduced risk of HBV-induced HCC in Asian.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Jemal, A., et al. (2011). Global cancer statistics. CA: A cancer journal for clinicians, 61(2), 69–90.

    Google Scholar 

  2. Perz, J. F., et al. (2006). The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. Journal of Hepatology, 45(4), 529–538.

    Article  PubMed  Google Scholar 

  3. Bowen, D. G., & Walker, C. M. (2005). Adaptive immune responses in acute and chronic hepatitis C virus infection. Nature, 436(7053), 946–952.

    Article  CAS  PubMed  Google Scholar 

  4. Chen, S. L., & Morgan, T. R. (2006). The natural history of hepatitis C virus (HCV) infection. International Journal of Medical Sciences, 3(2), 47–52.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Shen, F. M., et al. (1991). Complex segregation analysis of primary hepatocellular carcinoma in Chinese families: Interaction of inherited susceptibility and hepatitis B viral infection. American Journal of Human Genetics, 49(1), 88–93.

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Yu, M. W., et al. (2000). Familial risk of hepatocellular carcinoma among chronic hepatitis B carriers and their relatives. Journal of the National Cancer Institute, 92(14), 1159–1164.

    Article  CAS  PubMed  Google Scholar 

  7. Rane, S. G., & Reddy, E. P. (2000). Janus kinases: Components of multiple signaling pathways. Oncogene, 19(49), 5662–5679.

    Article  CAS  PubMed  Google Scholar 

  8. Ward, A. C., Touw, I., & Yoshimura, A. (2000). The Jak-Stat pathway in normal and perturbed hematopoiesis. Blood, 95(1), 19–29.

    CAS  PubMed  Google Scholar 

  9. Watford, W. T., et al. (2004). Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4. Immunology Review, 202, 139–156.

    Article  CAS  Google Scholar 

  10. Morinobu, A., et al. (2002). STAT4 serine phosphorylation is critical for IL-12-induced IFN-gamma production but not for cell proliferation. Proceedings of the National Academy of Sciences of the United States of America, 99(19), 12281–12286.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Nishikomori, R., et al. (2002). Activated STAT4 has an essential role in Th1 differentiation and proliferation that is independent of its role in the maintenance of IL-12R beta 2 chain expression and signaling. Journal of Immunology, 169(8), 4388–4398.

    Article  CAS  Google Scholar 

  12. Remmers, E. F., et al. (2007). STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. The New England Journal of Medicine, 357(10), 977–986.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Lee, H. S., et al. (2007). Association of STAT4 with rheumatoid arthritis in the Korean population. Molecular Medicine, 13(9–10), 455–460.

    CAS  PubMed Central  PubMed  Google Scholar 

  14. Clark, A., et al. (2013). A trivial role of STAT4 variant in chronic hepatitis B induced hepatocellular carcinoma. Infection, Genetics and Evolution, 18, 257–261.

    Article  CAS  PubMed  Google Scholar 

  15. Jiang, D. K., et al. (2013). Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma. Nature Genetics, 45(1), 72–75.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Higgins, J. P., & Thompson, S. G. (2002). Quantifying heterogeneity in a meta-analysis. Statistics in Medicine, 21(11), 1539–1558.

    Article  PubMed  Google Scholar 

  17. Begg, C. B., & Mazumdar, M. (1994). Operating characteristics of a rank correlation test for publication bias. Biometrics, 50(4), 1088–1101.

    Article  CAS  PubMed  Google Scholar 

  18. Egger, M., et al. (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315(7109), 629–634.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Bettelli, E., Oukka, M., & Kuchroo, V. K. (2007). T(H)-17 cells in the circle of immunity and autoimmunity. Nature Immunology, 8(4), 345–350.

    Article  CAS  PubMed  Google Scholar 

  20. Mathur, A. N., et al. (2007). Stat3 and Stat4 direct development of IL-17-secreting Th cells. Journal of Immunology, 178(8), 4901–4907.

    Article  CAS  Google Scholar 

  21. Kariuki, S. N., et al. (2009). Cutting edge: Autoimmune disease risk variant of STAT4 confers increased sensitivity to IFN-alpha in lupus patients in vivo. Journal of Immunology, 182(1), 34–38.

    Article  CAS  Google Scholar 

  22. Gao, X., et al. (2014). Association of cytotoxic T lymphocyte antigen-4 +49A/G polymorphism and cancer risk: An updated meta-analysis. Cancer biomarkers, 14(4), 287–294.

    CAS  PubMed  Google Scholar 

  23. He, J., et al. (2014) Influence of interleukin-28B polymorphism on progression to hepatitis virus-induced hepatocellular carcinoma. Tumour biology, 1–7. doi:10.1007/s13277-014-2142-3.

  24. Saxena, R., et al. (2014). IFN-gamma (+874) and not TNF-alpha (−308) is associated with HBV-HCC risk in India. Molecular and Cellular Biochemistry, 385(1–2), 297–307.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hospital & Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China

    Xiangqian Zhao, Kai Jiang, Bin Liang & Xiaoqiang Huang

Authors
  1. Xiangqian Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kai Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bin Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaoqiang Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiangqian Zhao.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, X., Jiang, K., Liang, B. et al. STAT4 Gene Polymorphism and Risk of Chronic Hepatitis B-Induced Hepatocellular Carcinoma. Cell Biochem Biophys 71, 353–357 (2015). https://doi.org/10.1007/s12013-014-0205-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-014-0205-0

Keywords

Search

Navigation