The relationship between hepatitis C - related hepatocellular carcinoma and IL-23 receptor gene polymorphism

Document Type : Scientific Research

Authors

1 Department of Gastroenterology and Hepatology, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt.

2 Department of Internal Medicine, Faculty of Medicine, Zagazig University, Egypt

3 Biochemistry department, faculty of medicine, zagazig university, Egypt

4 Medical Biochemistry, Faculty of Medicine, Zagazig University

5 Medical Oncology Department, Faculty of Medicine, Zagazig University

Abstract

Aims: This study evaluated the relationship between developing interleukin-23 receptor (IL- 23R) gene polymorphism and hepatitis C-related hepatocellular carcinoma (HCC) in Egyptian patients.
Patients & Methods: The current study included 250 subjects. They were divided into three groups: one hundred patients with hepatitis C virus (HCV) infection without HCC, one hundred patients with HCV and HCC, and fifty healthy non-hepatic volunteers as a control group. IL- 23R gene polymorphism (rs10889677) was genotyped by restriction fragment length polymorphism- polymerase chain reaction (RFLP- PCR).
Results: There was a significant difference between the studied groups regarding the frequency of genotypes and alleles (P =0.006 and < 0.001, respectively). Additionally, under the recessive inheritance model, IL-23R polymorphism is significantly associated with HCC development (P=0.001). Moreover, a significant protective effect of the rs10889677 C allele in HCC susceptibility was detected (OR = 0.15, 95% CI = 0.05–0.39, P < 0.001). AC and CC genotypes also had a significant protective effect (OR = 0.16, 95% CI = 0.05–0.46, P < 0.001). 
 Conclusions: there is a possible relationship between IL- 23R (rs10889677) polymorphism and HCC risk in Egyptian individuals where AC and CC genotypes and C alleles are protective.     

Keywords

Main Subjects

References

1. Ministry of Health and Population [Egypt], El-Zanaty and Associates [Egypt], ICF International Egypt Health Issues Survey 2015. Cairo, Rockville, MD: Ministry of Health and Population, ICF International; 2015. 2. Nguyen MH, Keeffe EB. Prevalence and treatment of hepatitis C virus genotype 4, 5, and 6. Clin Gastroenterol Hepatol. 2005; 3(10 Suppl 2): S97-S101. doi:10.1016/s1542-3565(05)00711-1 3. European Association for The Study of The Liver; European Organisation for Research and Treatment of Cancer. EASLEORTC clinical practice guidelines: management of hepatocellular carcinoma [published correction appears in J Hepatol. 2012 Jun; 56 (6):1430]. J Hepatol. 2012; 56(4):908-943. doi: 10.1016/j.jhep.2011.12.001 4. Karimkhanloo H, Mohammadi-Yeganeh S, Ahsani Z, Paryan M. Bioinformatics prediction and experimental validation of microRNA-20a targeting Cyclin D1 in hepatocellular carcinoma. Tumour Biol. 2017;39(4):1010428317698361. doi:10.1177/1010428317698361 5. Al-Qahtani AA, Al-Anazi M, Abdo AA, et al. Genetic variation at -1878 (rs2596542) in MICA gene region is associated with chronic hepatitis B virus infection in Saudi Arabian patients. Exp Mol Pathol. 2013;95(3):255-258. doi: 10.1016/j.yexmp.2013.08.005. 6. Yang YM, Kim SY, Seki E. Inflammation and Liver Cancer: Molecular Mechanisms and Therapeutic Targets. Semin Liver Dis. 2019;39(1):26-42. doi:10.1055/s-0038-1676806 7. Ma X, McKeen T, Zhang J, Ding WX. Role and Mechanisms of Mitophagy in Liver Diseases. Cells. 2020;9(4):837. Published 2020 Mar 31. doi:10.3390/cells9040837 8. Eken A, Singh AK, Treuting PM, Oukka M. IL-23R+ innate lymphoid cells induce colitis via interleukin-22-dependent mechanism. Mucosal Immunol. 2014;7(1):143-154. doi:10.1038/mi.2013.33 9. Dubinsky MC, Wang D, Picornell Y, et al. IL-23 receptor (IL-23R) gene protects against pediatric Crohn's disease. Inflamm Bowel Dis. 2007;13(5):511-515. doi:10.1002/ibd.20126 10. Xu Y, Liu Y, Pan S, et al. IL-23R polymorphisms, HBV infection, and risk of hepatocellular carcinoma in a high-risk Chinese population. J Gastroenterol. 2013;48(1):125-131. doi:10.1007/s00535-012-0620-1 11. Weersma RK, Zhernakova A, Nolte IM, et al. ATG16L1 and IL23R are associated with inflammatory bowel diseases but not celiac disease in the Netherlands. Am J Gastroenterol. 2008;103(3):621-627. doi:10.1111/j.1572-0241.2007. 01660.x 12. Song GG, Bae SC, Choi SJ, Ji JD, Lee YH. Associations between interleukin-23 receptor polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis. Mol Biol Rep. 2012;39(12):10655-10663. doi:10.1007/s11033-012-1955-7 13. Chen B, Zeng Z, Xu L, et al. IL23R +2199A/C polymorphism is associated with decreased risk of certain subtypes of gastric cancer in Chinese: a case-control study. Cancer Epidemiol. 2011;35(2):165-169. doi: 10.1016/j.canep.2010.08.006 14. Chien MH, Hsin CH, Chou LS, et al. Interleukin-23 receptor polymorphism as a risk factor for oral cancer susceptibility. Head Neck. 2012;34(4):551-556. doi:10.1002/hed.21779 15. Tarao K, Rino Y, Ohkawa S, et al. Association between high serum alanine aminotransferase levels and more rapid development and higher rate of incidence of hepatocellular carcinoma in patients with hepatitis C virus-associated cirrhosis. Cancer. 1999;86(4):589-595. 16. Yoshida H, Shiratori Y, Moriyama M, et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT Study Group. Inhibition of Hepatocarcinogenesis by Interferon Therapy. Ann Intern Med. 1999;131(3):174-181. doi:10.7326/0003-4819-131-3-199908030-00003 17. Parmiani G, Anichini A. T cell infiltration and prognosis in HCC patients. J Hepatol. 2006;45(2):178-181. doi: 10.1016/j.jhep.2006.06.005 18. Langowski JL, Zhang X, Wu L, et al. IL-23 promotes tumour incidence and growth. Nature. 2006;442(7101):461-465. doi:10.1038/nature04808 19. Volpe E, Servant N, Zollinger R, et al. A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses. Nat Immunol. 2008;9(6):650-657. doi:10.1038/ni.1613 20. Amer T, El-Baz R, Mokhtar AR, El-Shaer S, Elshazli R, Settin A. Genetic polymorphisms of IL-23R (rs7517847) and LEP (rs7799039) among Egyptian patients with hepatocellular carcinoma. Arch Physiol Biochem. 2017;123(5):279-285. doi:10.1080/13813455.2017.1320680 21. Pan X, Wang G. Correlations of IL-23R gene polymorphism with clinicopathological characteristics and prognosis of hepatocellular carcinoma patients after interventional therapy. Genomics. 2019;111(4):930-935. doi: 10.1016/j.ygeno.2018.05.023 22. Han R, Xia Q, Xu S, Fan D, Pan F. Interleukin-23 receptor polymorphism (rs10889677 A/C) in ankylosing spondylitis: Meta-analysis in Caucasian and Asian populations. Clin Chim Acta. 2018; 477:53-59. doi: 10.1016/j.cca.2017.11.038 23. Wendling D. Interleukin 23: a key cytokine in chronic inflammatory disease. Joint Bone Spine. 2008;75(5):517-519. doi: 10.1016/j.jbspin.2008.03.004 24. Voo KS, Wang YH, Santori FR, et al. Identification of IL-17-producing FOXP3+ regulatory T cells in humans. Proc Natl Acad Sci U S A. 2009;106(12):4793-4798. doi:10.1073/pnas.0900408106 25. Libioulle C, Louis E, Hansoul S, et al. Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4. PLoS Genet. 2007;3(4): e58. doi: 10.1371/journal.pgen.0030058 26. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299(5609):1057-1061. doi:10.1126/science.1079490 27. Kim JM, Rasmussen JP, Rudensky AY. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat Immunol. 2007;8(2):191-197. doi:10.1038/ni1428.
African Journal of Gastroenterology and Hepatology
Volume 5, Issue 1
January 2022
Pages 77-89

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