Skip to main content

Advertisement

SpringerLink
Log in

Role of host interleukin 1β gene (IL-1B) and interleukin 1 receptor antagonist gene (IL-1RN) polymorphisms in clinical outcomes in Helicobacter pylori-positive Turkish patients with dyspepsia

  • Alimmentary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Helicobacter pylori infection leads to different clinical outcomes depending on both host and bacterial factors. In a recent study, we identified H. pylori cagE and babA2 genotypes as independent predictors of duodenal ulcer (DU) and gastric cancer (GC) in dyspepsia patients, but no previous studies have examined the role of host-related genetic factors in Turkey. This time our aim was to evaluate whether polymorphisms of the interleukin 1B (IL-1B) and the interleukin 1 receptor antagonist (IL-1RN) genes are important factors in the differential expression of gastroduodenal diseases in H. pylori-positive dyspepsia patients.

Methods

Ninety-three H. pylori-positive patients, 30 with nonulcer dyspepsia (NUD), 30 with DU, and 33 with GC, were investigated. The IL-1B-511 and IL-1B-31 biallelic polymorphisms, and the IL-1RN intron 2 variable number tandem repeat were genotyped by polymerase chain reaction and single-strand confirmation polymorphism analysis.

Results

The IL-1RN-1/1 genotype was significantly more prevalent among patients with NUD than among those with GC (χ2 = 9.270; P = 0.002), and the IL-1RN-1/2 genotype was significantly more common in patients with GC (χ2 = 6.01; P = 0.014). Multivariate regression analysis showed that cagE, babA2, and IL-1RN-1/2 genotypes were independent predictors of GC, but when patients with benign disorders were grouped together (NUD + DU) and compared with patients with GC, regression analysis disclosed that babA2 (P = 0.000) and IL-1B-31 gene polymorphisms (CC or CT) (P = 0.01) were the only independent markers of GC.

Conclusions

When analyzed together with host genetic factors, the wellestablished bacterial risk factor babA2 seems to be the most important predictor of malignant disorders, and the presence of the IL-1B-31TT genotype emerges as a protective factor against them.

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

Similar content being viewed by others

References

  1. Blaser MJ. Ecology of Helicobacter pylori in the human stomach. J Clin Invest 1997;100:759–762.

    Article  PubMed  CAS  Google Scholar 

  2. Correa P. Human gastric carcinogenesis: a multistep and multifactorial process. First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res 1992;52:6735–6740.

    PubMed  CAS  Google Scholar 

  3. Blaser MJ. Linking Helicobacter pylori to gastric cancer. Nat Med 2000;6:376–377.

    Article  PubMed  CAS  Google Scholar 

  4. Peek RM, Blaser MJ. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer 2002;2:28–37.

    Article  PubMed  CAS  Google Scholar 

  5. Mobley HL. Defining Helicobacter pylori as a pathogen: strain heterogeneity and virulence. Am J Med 1996;100:2S–9S.

    Article  PubMed  CAS  Google Scholar 

  6. Atherton JC. The clinical relevance of strain types of Helicobacter pylori. Gut 1997;40:701–703.

    Article  PubMed  CAS  Google Scholar 

  7. El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 2000;404:398–402.

    Article  PubMed  CAS  Google Scholar 

  8. Machado JC, Pharoah P, Sousa S, Carvalho R, Oliveira C, Figueiredo C, et al. Interleukin-1b and interleukin-1RN polymorphisms are associated with increased risk of gastric carcinoma. Gastroenterology 2001;121:823–829.

    Article  PubMed  CAS  Google Scholar 

  9. Noach LA, Bosma NB, Jansen J, Hoek FJ, van Deventer SJ, Tytgat GN. Mucosal tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8 production in patients with Helicobacter pylori infection. Scand J Gastroenterol 1994;29:425–429.

    Article  PubMed  CAS  Google Scholar 

  10. Basso D, Scrigner M, Toma A, Navaglia F, Di Mario F, Rugge M, et al. Helicobacter pylori infection enhances mucosal interleukin-1 beta, interleukin-6, and the soluble receptor of interleukin-2. Int J Clin Lab Res 1996;26:207–210.

    Article  PubMed  CAS  Google Scholar 

  11. Arend WP, Malyak M, Guthridge CJ, Gabay C. Interleukin-1 receptor antagonist: role in biology. Annu Rev Immunol 1998;16:27–55.

    Article  PubMed  CAS  Google Scholar 

  12. Santtila S, Savinainen K, Hurme M. Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro. Scand J Immunol 1998;47:195–198.

    Article  PubMed  CAS  Google Scholar 

  13. Danis VA, Millington M, Hyland VJ, Grennan D. Cytokine production by normal human monocytes: inter-subject variation and relationship to an IL-1 receptor antagonist (IL-1Ra) gene polymorphism. Clin Exp Immunol 1995;99:303–310.

    PubMed  CAS  Google Scholar 

  14. El-Omar EM. The importance of interleukin-1beta in Helicobacter pylori associated disease. Gut 2001;48:743–747.

    Article  PubMed  CAS  Google Scholar 

  15. Koivurova OP, Karhukorpi JM, Joensuu ET, Koistinen PO, Valtonen JM, Karttunen TJ, et al. IL-1 RN 2/2 genotype and simultaneous carriage of genotypes IL-1 RN 2/2 and IL-1beta-511 T/T associated with oesophagitis in Helicobacter pylori-negative patients. Scand J Gastroenterol 2003;38:1217–1222.

    Article  PubMed  CAS  Google Scholar 

  16. Tahara E. Genetic pathways of two types of gastric cancer. IARC Sci Pub 2004;157:327–349.

    Google Scholar 

  17. Furuta T, Shirai N, Sugimoto M. Controversy in polymorphisms of interleukin-1beta in gastric cancer risks. J Gastroenterol 2004;39:501–503.

    Article  PubMed  Google Scholar 

  18. Erzin Y, Koksal V, Altun S, Dobrucali A, Aslan M, Erdamar S, et al. Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA, babA2 genotypes and correlation with clinical outcome in Turkish patients with dyspepsia. Helicobacter 2006;11:574–580.

    Article  PubMed  CAS  Google Scholar 

  19. Shields PG, Haris CC. Cancer risk and low-penetrance susceptibility genes in gene-environment interactions. J Clin Oncol 2000;18:2309–2315.

    PubMed  CAS  Google Scholar 

  20. Erichsen HC, Chanock SJ. SNPs in cancer research and treatment. Br J Cancer 2004;90:747–751.

    Article  PubMed  CAS  Google Scholar 

  21. Gonzales CA, Sala N, Capella G. Genetic susceptibility and gastric cancer risk. Int J Cancer 2004;100:249–260.

    Article  CAS  Google Scholar 

  22. Figueiredo C, Machado JC, Pharoah P, Seruca R, Sousa S, Carvalho R, et al. Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Inst 2002;94:1680–1687.

    PubMed  CAS  Google Scholar 

  23. Ruzzo A, Graziano F, Pizzagalli F, Santini D, Battistelli V, Panunzi S, et al. Interleukin 1B gene (IL-1B) and interleukin 1 receptor antagonist gene (IL-1RN) polymorphism in Helicobacter pylori-negative gastric cancer of intestinal and diffuse histotype. Ann Oncol 2005;16:887–892.

    Article  PubMed  CAS  Google Scholar 

  24. Karaoguz H, Icli F. Cancer Problem in Turkiye. J Ankara Med School 1993;15:547–558.

    Google Scholar 

  25. World Health Organization. World cancer report. Geneva, Switzerland: International Agency for Research on Cancer; 2003.

    Google Scholar 

  26. Kato S, Onda M, Yamada S, Matsuda N, Tokunaga A, Matsukura N. Association of the interleukin-1β genetic polymorphism and gastric cancer risk in Japanese. J Gastroenterol 2001;36:696–699.

    Article  PubMed  CAS  Google Scholar 

  27. Lee SG, Kin B, Choi WY, Lee IC, Choi JW, Song KY. Lack of association between pro-inflammatory genotypes of the interleukin-1 (IL-1B-31C/+ and IL-1RN*2/*2) and gastric cancer/duodenal ulcer in Korean population. Cytokine 2003;21:167–171.

    Article  PubMed  CAS  Google Scholar 

  28. Hamajima N, Matsuo K, Saito T, Tajima K, Okuma K, Yamao K, et al. Interleukin 1 polymorphisms, lifestyle factors, and Helicobacter pylori infection. Jpn J Cancer Res 2001;92:383–389.

    PubMed  CAS  Google Scholar 

  29. Lee S, Hong S, Yoon Y, Yang I, Song K. Characterization of publicly available SNPs in the Korean population. Hum Mutat 2001;17:281–284.

    Article  PubMed  CAS  Google Scholar 

  30. Ertem D, Harmanci H, Pehlivanoglu E. Helicobacter pylori infection in Turkish preschool and school children: role of socioeconomic factors and breast feeding. Turk J Pediatr 2003;45:114–122.

    PubMed  Google Scholar 

  31. Us D, Hascelik G. Seroprevalence of Helicobacter pylori infection in an asymptomatic Turkish population. J Infect 1998;37:148–150.

    Article  PubMed  CAS  Google Scholar 

  32. Suerbaum S, Michetti P. Helicobacter pylori infection. N Engl J Med 2002;347:1175–1186.

    Article  PubMed  CAS  Google Scholar 

  33. Schistosomes, liver flukes and Helicobacter pylori. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, Lyon, 7–14 June 1994. IARC Monogr Eval Carcinog Risks Hum 1994;61:1–241.

  34. Bretagne JF.Could Helicobacter pylori treatment reduce stomach cancer risk? Gastroenterol Clin Biol 2003;27:440–452.

    Google Scholar 

  35. Hunt RH, Fallone C, Veldhuyzen VZ, Sherman P, Smaill F, Thomson AB. Risks and benefits of Helicobacter pylori eradication: current status. Can J Gastroenterol 2002;16:57–62.

    PubMed  Google Scholar 

  36. Fendrick AM, Chernew ME, Hirth RA, Bloom BS, Bandekar RR, Scheiman JM. Clinical and economic effects of populationbased Helicobacter pylori screening to prevent gastric cancer. Arch Intern Med 1999;159:142–148.

    Article  PubMed  CAS  Google Scholar 

  37. Parsonnet J, Haris RA, Hack HM, Owens DK. Modeling costeffectiveness of Helicobacter pylori screening to prevent gastric cancer: a mandate for clinical trials. Lancet 1996;348:150–154.

    Article  PubMed  CAS  Google Scholar 

  38. Malfertheiner P, Megraud F, O’Morain C, Bazzoli F, El-Omar E, Graham D, et al. Current concepts in the management of Helicobacter pylori infection: the Maastricht Consensus Report. Aliment Pharmacol Ther 2002;16:167–180.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey

    Yusuf Erzin & Ahmet Dobrucali

  2. Burc Molecular Genetic Diagnosis and Research Center, Istanbul, Turkey

    Vedat Koksal

  3. Department of Microbiology and Clinical Microbiology, Istanbul University, Cerrahpasa Medical Faculty, 34 303, Kocamustafapasa, Istanbul, Turkey

    Sibel Altun, Mustafa Aslan & Bekir Kocazeybek

  4. Department of Pathology, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey

    Sibel Erdamar & SÜha Goksel

  5. Department of Biostatistics, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey

    Ahmet Dirican

Authors
  1. Yusuf Erzin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vedat Koksal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sibel Altun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ahmet Dobrucali
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mustafa Aslan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sibel Erdamar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. SÜha Goksel
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ahmet Dirican
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bekir Kocazeybek
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Erzin, Y., Koksal, V., Altun, S. et al. Role of host interleukin 1β gene (IL-1B) and interleukin 1 receptor antagonist gene (IL-1RN) polymorphisms in clinical outcomes in Helicobacter pylori-positive Turkish patients with dyspepsia. J Gastroenterol 43, 705–710 (2008). https://doi.org/10.1007/s00535-008-2220-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-008-2220-7

Key words

Search

Navigation