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2014, Number 6

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Ann Hepatol 2014; 13 (6)

The role of Interleukin 28B gene polymorphism in Turkish patients with hepatocellular carcinoma

Akkiz H, Kuran S, Akgöllü E, Üsküdar O, Bekar A, Bayram S

Language: English
References: 34
Page: 788-795
PDF size: 117.22 Kb.


ABSTRACT

Background and aim. Multiple risk factors lead to hepatocellular carcinoma (HCC) including viral infections, mutation and single nucleotide polymorphisms (SNPs). Interleukin 28B (IL28B) gene rs12979860 polymorphism has been shown to be associated with HCC in the different populations, but its association with HCC has not been investigated in the Turkish population. We investigated whether the rs12979860 polymorphism of IL28B gene affects the risk of HCC. Material and method. We performed genotyping analysis using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a hospital-based case-control study of 187 confirmed HCC patients and 208 healthy subjects (cancer and viral infection negative) in the Turkish population. Results. The allele and genotype analysis showed no significant differences between the risk of HCC and IL28B gene rs12979860 polymorphism (OR = 1.10; 95% 0.59-2.08 P = 0.76 for genotype). However, in the HBV-related HCC subgroup, the TT genotype increased a 1.46-fold the risk of developing HCC, but not statistically significant (OR = 1.46; 95% 0.71-2.97 P = 0.30). Furthermore, no significant differences were found between clinical findings, and sex in comparison with the IL28B genotypes in HCC group (P › 0.05). Conclusion. Our results suggest, for the first time, that no significant association were found between IL28B rs12979860 genotypes with the risk of developing HCC in Turkish patients. Further independent investigations are required to clarify the possible role of IL28B gene rs12979860 polymorphism on the risk of developing HCC in a larger series and also in patients of different ethnic origins.


REFERENCES

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61: 69-90.

  2. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55: 74-108.

  3. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007; 132: 2557-76.

  4. Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 2006; 6: 674-87.

  5. Akkiz H, Bayram S, Bekar A, Akgöllü E, Ulger Y. A functional polymorphism in pre-microRNA-196a-2 contributes to the susceptibility of hepatocellular carcinoma in a Turkish population: a case-control study. J Viral Hepat 2011; 18: e399-e407.

  6. Li M, Liu X, Zhou Y, Su SB. Interferon-lambdas: the modulators of antivirus, antitumor, and immune responses. J Leukoc Biol 2009; 86: 23-32. 795 IL28 gene polymorphism and HCC. , 2014; 13 (6): 788-795

  7. Marcello T, Grakoui A, Barba-Spaeth G, Machlin ES, Kotenko SV, MacDonald MR, Rice CM. Interferons alpha and lambda inhibit hepatitis C virus replication with distinc signal transduction and gene regulation genetics. Gastroenterology 2006; 131: 1887-98.

  8. Langhans B, Kupfer B, Braunschweiger I, Arndt S, Schulte W, Nischalke HD, Nattermann J, et al. Interferon-lambda serum levels in hepatitis C. J Hepatol 2011; 54: 859-65.

  9. Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, O’Huigin C, Kidd J, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 2009; 461: 798-801.

  10. Sugiyama M, Tanaka Y, Nakanishi M, Mizokami M. Novel findings for the development of drug therapy for various liver diseases: genetic variation in IL-28B is associated with response to the therapy for chronic hepatitis C. J Pharmacol Sci 2011; 115: 263-9.

  11. Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, et al. Genetic variation in IL28B predicts hepatitis C treatment induced viral clearance. Nature 2009; 461: 399-401.

  12. Li W, Lewis-Antes A, Huang J, Balan M, Kotenko SV. Regulation of apoptosis by type III interferons. Cell Prolif 2008; 41: 960-79.

  13. Numasaki M, Tagawa M, Iwata F, Suzuki T, Nakamura A, Okada M, Iwakura Y, et al. IL-28 elicits antitumor responses against murine fibrosarcoma. J Immunol 2007; 178: 5086-98.

  14. Maher SG, Sheikh F, Scarzello AJ, Romero-Weaver AL, Baker DP, Donnelly RP, Gamero AM, et al. IFNalpha and IFNlambda differ in their antiproliferative effects and duration of JAK/STAT signaling activity. Cancer Biol Ther 2008; 7: 1109–15.

  15. Chen J, Wang L, Li Y, Cai B, Fu Y, Liao Y, Zhang J. Association analysis between SNPs in IL-28B gene and the progress of hepatitis B infection in Han Chinese. PLoS One 2012; 7: e50787.

  16. Eurich D, Boas-Knoop S, Bahra M, Neuhaus R, Somasundaram R, Neuhaus P, Neumann U, et al. Role of IL28B polymorphism in the development of hepatitis C virus-induced hepatocellular carcinoma, graft fibrosis, and posttransplant antiviral therapy. Transplantation 2012; 93: 644-9.

  17. Fabris C, Falleti E, Cussigh A, Bitetto D, Fontanini E, Bignulin S, Cmet S, et al. IL-28B rs12979860 C/T allele distribution in patients with liver cirrhosis: role in the course of chronic viral hepatitis and the development of HCC. J Hepatol 2011; 54: 716-22.

  18. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona- 2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001; 35: 421-30.

  19. Tsai JF, Chang WY, Jeng JE, Ho MS, Lin ZY, Tsai JH. Hepatitis B and C virus infection as risk factors for liver cirrhosis and cirrhotic hepatocellular carcinoma: a case-control study. Liver 1994; 14: 98-102.

  20. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the esophagus for bleeding esophageal varices. Br J Surg 1973; 60: 646-9.

  21. Kim YJ, Lee HS. Single nucleotide polymorphisms associated with hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Intervirology 2005; 48: 10-5.

  22. Kato N, Ji G, Wang Y, Baba M, Hoshida Y, Otsuka M, Taniguchi H, et al. Large-scale search of single nucleotide polymorphisms for hepatocellular carcinoma susceptibility genes in patients with hepatitis C. Hepatology 2005; 42: 846-53.

  23. Ludwig JA, Weinstein JN. Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer 2005; 5: 845-56.

  24. Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, Bassendine M, et al. IL28B is associated with response to chronic hepatitis C interferon-a and ribavirin therapy. Nat Genet 2009; 41: 1100-4.

  25. Honda M, Sakai A, Yamashita T, Nakamoto Y, Mizukoshi E, Sakai Y, Yamashita T, et al. Hepatic ISG expression is associated with genetic variation in interleukin 28B and the outcome of IFN therapy for chronic hepatitis C. Gastroenterology 2010; 139: 499-509.

  26. Sakamoto N, Nakagawa M, Tanaka Y, Sekine-Osajima Y, Ueyama M, Kurosaki M, Nishida N, et al. Association of IL28B variants with response to pegylated-interferon alpha plus ribavirin combination therapy reveals intersubgenotypic differences between genotypes 2a and 2b. J Med Virol 2011; 83: 871-8.

  27. Fischer J, Böhm S, Scholz M, Müller T, Witt H, George J, Sarrazin C, et al. Combined effects of different interleukin- 28B gene variants on the outcome of dual combination therapy in chronic hepatitis C virus type 1 infection. Hepatology 2012; 55: 1700-10.

  28. Li Q, Kawamura K, Ma G, Iwata F, Numasaki M, Suzuki N, Shimada H, et al. Interferon-lambda induces G1 phase arrest or apoptosis in oesophageal carcinoma cells and produces anti-tumour effects in combination with anti-cancer agents. Eur J Cancer 2010; 46: 180-90.

  29. Zitzmann K, Brand S, Baehs S, Göke B, Meinecke J, Spöttl G, Meyer H, et al. Novel interferon-lambdas induce antiproliferative effects in neuroendocrine tumor cells. Biochem Biophys Res Commun 2006; 344: 1334-41.

  30. Sato A, Ohtsuki M, Hata M, Kobayashi E, Murakami T. Antitumor activity of IFN-lambda in murine tumor models. J Immunol 2006; 176(12): 7686-94.

  31. Ezzikouri S, Alaoui R, Rebbani K, Brahim I, Fakhir FZ, Nadir S, Diepolder H, et al. Genetic variation in the interleukin- 28B gene is associated with spontaneous clearance and progression of hepatitis C virus in Moroccan patients. PLoS One 2013; 8: e54793.

  32. Agúndez JA, García-Martin E, Maestro ML, Cuenca F, Martínez C, Ortega L, Carballo M, et al. Relation of IL28B gene polymorphism with biochemical and histological features in hepatitis C virus-induced liver disease. PLoS One 2012; 7: e37998.

  33. Ren S, Lu J, Du X, Huang Y, Ma L, Huo H, Chen X, et al. Genetic variation in IL28B is associated with the development of hepatitis B-related hepatocellular carcinoma. Cancer Immunol Immunother 2012; 61: 1433-9.

  34. Lee DH, Cho Y, Seo JY, Kwon JH, Cho EJ, Jang ES, Kwak MS, et al. Polymorphisms near interleukin 28B gene are not associated with hepatitis B virus clearance, hepatitis B e antigen clearance and hepatocellular carcinoma occurrence. Intervirology 2013; 56: 84-90.




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