1887

Abstract

Geographical variation in the frequency of various gastroduodenal pathologies was shown to be related to the geographical diversity of CagA Glu-Pro-Ile-Tyr-Ala (EPIYA) patterns. We examined the EPIYA patterns of and the association of EPIYA patterns with gastric cancer (GC) for the first time, to the best of our knowledge, in Turkey. The patient group (PG) contained 60 patients [38 GC and 22 duodenal ulcer (DU) patients]. The control group (CG) was 110 individuals [94 gastritis patients and 16 persons with a normal gastrointestinal system (NGIS)]. Specific primers were used for the detection of including empty-site-positive and EPIYA-A, -B, -C, -D PCR. Bands of EPIYA-A, -B, -C were confirmed by DNA sequencing. One hundred and forty-two (83.5 %) strains [60 in the PG (38 GC, 22 DU), 82 in the CG (72 gastritis, 10 NGIS)] were positive for the gene. EPIYA-C with multiple repeats was detected in 34 (23.9 %) strains, and 22 (64.7 %) were from GC patients. EPIYA-C with one repeat was detected in 89 (62.7 %) strains, and 54 (60.7 %) were from gastritis patients. EPIYT was detected in 10 strains, and EPIYA-D was not detected. The number of EPIYA-C with multiple repeats was significantly higher for the PG than for the CG ( < 0.0001). In GC patients, the number of EPIYA-C with multiple repeats was significantly higher than one repeat ( < 0.0001). In conclusion, our study showed that multiple EPIYA-C repeats increases the GC risk by 30.6-fold and the DU risk by 8.9-fold versus the CG. This indicates that Western-type strains in Turkey have similar EPIYA motifs to those of neighbouring countries and Western populations.

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2015-10-01
2019-10-17
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References

  1. Acosta N. , Quiroga A. , Delgado P. , Bravo M. M. , Jaramillo C. . ( 2010;). Helicobacter pylori CagA protein polymorphisms and their lack of association with pathogenesis. World J Gastroenterol 16: 3936–3943 [CrossRef] [PubMed].
    [Google Scholar]
  2. Ajami A. , Shadman M. , Rafiei A. , Hosseini V. , Talebi-Bezmin Abadi A. , Alizadeh A. , Hosseini-Khah Z. . ( 2013;). Prevalence of EPIYA motifs in Helicobacter pylori strains isolated from patients with dyspeptic disorders in Northern Iran. Res Mol Med 1: 29–34.
    [Google Scholar]
  3. Akopyants N. S. , Clifton S. W. , Kersulyte D. , Crabtree J. E. , Youree B. E. , Reece C. A. , Bukanov N. O. , Drazek E. S. , Roe B. A. , Berg D. E. . ( 1998;). Analyses of the cag pathogenicity island of Helicobacter pylori . Mol Microbiol 28: 37–53 [CrossRef] [PubMed].
    [Google Scholar]
  4. Argent R. H. , Kidd M. , Owen R. J. , Thomas R. J. , Limb M. C. , Atherton J. C. . ( 2004;). Determinants and consequences of different levels of CagA phosphorylation for clinical isolates of Helicobacter pylori . Gastroenterology 127: 514–523 [CrossRef] [PubMed].
    [Google Scholar]
  5. Argent R. H. , Zhang Y. , Atherton J. C. . ( 2005;). Simple method for determination of the number of Helicobacter pylori CagA variable-region EPIYA tyrosine phosphorylation motifs by PCR. J Clin Microbiol 43: 791–795 [CrossRef] [PubMed].
    [Google Scholar]
  6. Atherton J. C. . ( 2006;). The pathogenesis of Helicobacter pylori-induced gastro-duodenal diseases. Annu Rev Pathol 1: 63–96 [CrossRef] [PubMed].
    [Google Scholar]
  7. Atherton J. C. , Cao P. , Peek R. M. Jr , Tummuru M. K. , Blaser M. J. , Cover T. L. . ( 1995;). Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem 270: 17771–17777 [CrossRef] [PubMed].
    [Google Scholar]
  8. Azuma T. , Yamakawa A. , Yamazaki S. , Fukuta K. , Ohtani M. , Ito Y. , Dojo M. , Yamazaki Y. , Kuriyama M. . ( 2002;). Correlation between variation of the 3′ region of the cagA gene in Helicobacter pylori and disease outcome in Japan. J Infect Dis 186: 1621–1630 [CrossRef] [PubMed].
    [Google Scholar]
  9. Basara B. B. , Guler B. , Yentur G. K. , Birge G. , Pulgat E. , Ekinci B. M. . ( 2013;). Health statistics yearbook (2012) Turkey: Ministry of Health; http://www.sb.gov.tr/TR/dosya/1-87578/h/ıstaturk2012.
    [Google Scholar]
  10. Basso D. , Zambon C. F. , Letley D. P. , Stranges A. , Marchet A. , Rhead J. L. , Schiavon S. , Guariso G. , Ceroti M. , other authors . ( 2008;). Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms. Gastroenterology 135: 91–99 [CrossRef] [PubMed].
    [Google Scholar]
  11. Batista S. A. , Rocha G. A. , Rocha A. M. , Saraiva I. E. , Cabral M. M. , Oliveira R. C. , Queiroz D. M. . ( 2011;). Higher number of Helicobacter pylori CagA EPIYA C phosphorylation sites increases the risk of gastric cancer, but not duodenal ulcer. BMC Microbiol 11: 61 [CrossRef] [PubMed].
    [Google Scholar]
  12. Celik S. , Yılmaz E. M. , Özden F. , Kotan C. , Okut H. . ( 2015;). The relationship between eating and lifestyle habits and cancer in Van Lake region: another endemic region for esophageal and gastric cancers. J Cancer Epidemiol 2015: 254823 [CrossRef] [PubMed].
    [Google Scholar]
  13. Cendron L. , Couturier M. , Angelini A. , Barison N. , Stein M. , Zanotti G. . ( 2009;). The Helicobacter pylori CagD (HP0545, Cag24) protein is essential for CagA translocation and maximal induction of interleukin-8 secretion. J Mol Biol 386: 204–217 [CrossRef] [PubMed].
    [Google Scholar]
  14. Erzin Y. , Koksal V. , Altun S. , Dobrucali A. , Aslan M. , Erdamar S. , Dirican A. , Kocazeybek B. . ( 2006;). Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA and babA2 genotypes and correlation with clinical outcome in Turkish patients with dyspepsia. Helicobacter 11: 574–580 [CrossRef] [PubMed].
    [Google Scholar]
  15. Gücin Z. , Cakmak T. , Bayyurt N. , Salih B. . ( 2013;). Helicobacter pylori infection and relationship with gastric epithelial cell proliferation and apoptosis. Turk J Med Sci 43: 739–746 [CrossRef].
    [Google Scholar]
  16. Hatakeyama M. . ( 2004;). Oncogenic mechanisms of the Helicobacter pylori CagA protein. Nat Rev Cancer 4: 688–694 [CrossRef] [PubMed].
    [Google Scholar]
  17. He Q. , Wang J. P. , Osato M. , Lachman L. B. . ( 2002;). Real-time quantitative PCR for detection of Helicobacter pylori . J Clin Microbiol 40: 3720–3728 [CrossRef] [PubMed].
    [Google Scholar]
  18. Higashi H. , Tsutsumi R. , Muto S. , Sugiyama T. , Azuma T. , Asaka M. , Hatakeyama M. . ( 2002;). SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori Cag protein. Science 295: 683–686.[CrossRef]
    [Google Scholar]
  19. Huang J. Q. , Zheng G. F. , Sumanac K. , Irvine E. J. , Hunt R. H. . ( 2003;). Meta-analysis of the relationship between cagA seropositivity and gastric cancer. Gastroenterology 125: 1636–1644 [CrossRef] [PubMed].
    [Google Scholar]
  20. International Agency for Research on Cancer ( 1994;). Schistosomes, liver flukes and Helicobacter pylori . IARC Monogr Eval Carcin Risks Hum 61: 177–241.
    [Google Scholar]
  21. Jones K. R. , Joo Y. M. , Jang S. , Yoo Y. J. , Lee H. S. , Chung I. S. , Olsen C. H. , Whitmire J. M. , Merrell D. S. , Cha J. H. . ( 2009;). Polymorphism in the CagA EPIYA motif impacts development of gastric cancer. J Clin Microbiol 47: 959–968 [CrossRef] [PubMed].
    [Google Scholar]
  22. Kalaf E. A. , Al-Khafaji Z. M. , Yassen N. Y. , Al-Abbudi F. A. , Sadwen S. N. . ( 2013;). Study of the cytoxin-associated gene a (CagA gene) in Helicobacter pylori using gastric biopsies of Iraqi patients. Saudi J Gastroenterol 19: 69–74 [CrossRef] [PubMed].
    [Google Scholar]
  23. Kolaylı F. , Karadenizli A. , Bingöl R. , Schneider T. , Kist M. . ( 2012;). [Differences of vacA alleles and cagA gene positivity of Helicobacter pylori strains isolated from two different countries: Turkey and Germany]. Mikrobiyol Bul 46: 332–334 (in Turkey) [PubMed].
    [Google Scholar]
  24. Kucukoner M. , Balakan O. , Kaplan M. A. , Inal A. , Alabalik U. , Urakcı1 Z. , Dal M. S. , Yildiz Y. , Isikdogan A. . ( 2013;). Helicobacter pylori in primary gastric lymphoma and gastric cancer: A clinicopathologic and prognostic assessment. J Microbiol Infect Dis 3: 61–66 [CrossRef].
    [Google Scholar]
  25. Lima V. P. , Silva-Fernandes I. J. , Alves M. K. , Rabenhorst S. H. . ( 2011;). Prevalence of Helicobacter pylori genotypes (vacA, cagA, cagE and virB11) in gastric cancer in Brazilian's patients: an association with histopathological parameters. Cancer Epidemiol 35: e32–e37 [CrossRef] [PubMed].
    [Google Scholar]
  26. Malaty H. M. . ( 2007;). Epidemiology of Helicobacter pylori infection. Best Pract Res Clin Gastroenterol 21: 205–214 [CrossRef] [PubMed].
    [Google Scholar]
  27. Nagiyev T. , Yula E. , Abayli B. , Koksal F. . ( 2009;). Prevalence and genotypes of Helicobacter pylori in gastric biopsy specimens from patients with gastroduodenal pathologies in the Cukurova Region of Turkey. J Clin Microbiol 47: 4150–4153 [CrossRef] [PubMed].
    [Google Scholar]
  28. Occhialini A. , Marais A. , Urdaci M. , Sierra R. , Muñoz N. , Covacci A. , Mégraud F. . ( 2001;). Composition and gene expression of the cag pathogenicity island in Helicobacter pylori strains isolated from gastric carcinoma and gastritis patients in Costa Rica. Infect Immun 69: 1902–1908 [CrossRef] [PubMed].
    [Google Scholar]
  29. Ozbey G. , Dogan Y. , Demiroren K. . ( 2013;). Prevalence of Helicobacter pylori virulence genotypes among children in Eastern Turkey. World J Gastroenterol 19: 6585–6589 [CrossRef] [PubMed].
    [Google Scholar]
  30. Panayotopoulou E. G. , Sgouras D. N. , Papadakos K. , Kalliaropoulos A. , Papatheodoridis G. , Mentis A. F. , Archimandritis A. J. . ( 2007;). Strategy to characterize the number and type of repeating EPIYA phosphorylation motifs in the carboxyl terminus of cagA protein in Helicobacter pylori clinical isolates. J Clin Microbiol 45: 488–495 [CrossRef] [PubMed].
    [Google Scholar]
  31. Papadakos K. S. , Sougleri I. S. , Mentis A. F. , Hatziloukas E. , Sgouras D. N. . ( 2013;). Presence of terminal EPIYA phosphorylation motifs in Helicobacter pylori CagA contributes to IL-8 secretion, irrespective of the number of repeats. PLoS One 8: e56291 [CrossRef] [PubMed].
    [Google Scholar]
  32. Qadri Q. , Afroze D. , Rasool R. , Gulzar G. M. , Naqash S. , Siddiqi M. A. , Shah Z. A. . ( 2014;). CagA subtyping in Helicobacter pylori isolates from gastric cancer patients in an ethnic Kashmiri population. Microb Pathog 66: 40–43 [CrossRef] [PubMed].
    [Google Scholar]
  33. Sahara S. , Sugimoto M. , Vilaichone R. K. , Mahachai V. , Miyajima H. , Furuta T. , Yamaoka Y. . ( 2012;). Role of Helicobacter pylori cagA EPIYA motif and vacA genotypes for the development of gastrointestinal diseases in Southeast Asian countries: a meta-analysis. BMC Infect Dis 12: 223 [CrossRef] [PubMed].
    [Google Scholar]
  34. Salih B. A. , Bolek B. K. , Arikan S. . ( 2010;). DNA sequence analysis of cagA 3′ motifs of Helicobacter pylori strains from patients with peptic ulcer diseases. J Med Microbiol 59: 144–148 [CrossRef] [PubMed].
    [Google Scholar]
  35. Salih B. A. , Guner A. , Karademir A. , Uslu M. , Ovali M. A. , Yazici D. , Bolek B. K. , Arikan S. . ( 2014;). Evaluation of the effect of cagPAI genes of Helicobacter pylori on AGS epithelial cell morphology and IL-8 secretion. Antonie van Leeuwenhoek 105: 179–189 [CrossRef] [PubMed].
    [Google Scholar]
  36. Shokrzadeh L. , Baghaei K. , Yamaoka Y. , Dabiri H. , Jafari F. , Sahebekhtiari N. , Tahami A. , Sugimoto M. , Zojaji H. , Zali M. R. . ( 2010;). Analysis of 3′-end variable region of the cagA gene in Helicobacter pylori isolated from Iranian population. J Gastroenterol Hepatol 25: 172–177 [CrossRef] [PubMed].
    [Google Scholar]
  37. Sicinschi L. A. , Correa P. , Peek R. M. , Camargo M. C. , Piazuelo M. B. , Romero-Gallo J. , Hobbs S. S. , Krishna U. , Delgado A. , other authors . ( 2010;). CagA C-terminal variations in Helicobacter pylori strains from Colombian patients with gastric precancerous lesions. Clin Microbiol Infect 16: 369–378 [CrossRef] [PubMed].
    [Google Scholar]
  38. Silva A. V. , Silva Jr.R.M. , Vinagre R. M. D. F. , Santos K. N. , Costa R. A. A. , Fecury A. A. , Quaresma J. A. S. , Martins L. C. . ( 2014;). Evaluation of the pattern of EPIYA motifs in the Helicobacter pylori cagA gene of patients with gastritis and gastric adenocarcinoma from the Brazilian Amazon region. International Journal of Bacteriology 2014: 418063 [CrossRef].
    [Google Scholar]
  39. Suzuki H. , Moayyedi P. . ( 2013;). Helicobacter pylori infection in functional dyspepsia. Nat Rev Gastroenterol Hepatol 10: 168–174 [CrossRef] [PubMed].
    [Google Scholar]
  40. Torres L. E. , González L. , Melián K. , Alonso J. , Moreno A. , Hernández M. , Reyes O. , Bermúdez L. , Campos J. , other authors . ( 2012;). EPIYA motif patterns among Cuban Helicobacter pylori CagA positive strains. Biomedica 32: 23–31 [PubMed].
    [Google Scholar]
  41. Tsutsumi R. , Higashi H. , Higuchi M. , Okada M. , Hatakeyama M. . ( 2003;). Attenuation of Helicobacter pylori CagA–SHP-2 signaling by interaction between CagA and C-terminal Src kinase. J Biol Chem 278: 3664–3670 [CrossRef] [PubMed].
    [Google Scholar]
  42. van Doorn L. J. , Figueiredo C. , Rossau R. , Jannes G. , van Asbroek M. , Sousa J. C. , Carneiro F. , Quint W. G. . ( 1998;). Typing of Helicobacter pylori vacA gene and detection of cagA gene by PCR and reverse hybridization. J Clin Microbiol 36: 1271–1276 [PubMed].
    [Google Scholar]
  43. Vaziri F. , Najar Peerayeh S. , Alebouyeh M. , Molaei M. , Maghsoudi N. , Zali M. R. . ( 2013;). Determination of Helicobacter pylori CagA EPIYA types in Iranian isolates with different gastroduodenal disorders. Infect Genet Evol 17: 101–105 [CrossRef] [PubMed].
    [Google Scholar]
  44. Vaziri F. , Peerayeh S. N. , Alebouyeh M. , Maghsoudi N. , Azimzadeh P. , Siadat S. D. , Zali M. R. . ( 2015;). Novel effects of Helicobacter pylori CagA on key genes of gastric cancer signal transduction: a comparative transfection study. Pathog Dis 73: ftu021 [CrossRef] [PubMed].
    [Google Scholar]
  45. Wroblewski L. E. , Peek R. M. Jr , Wilson K. T. . ( 2010;). Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev 23: 713–739 [CrossRef] [PubMed].
    [Google Scholar]
  46. Yamaoka Y. . ( 2010;). Mechanisms of disease: Helicobacter pylori virulence factors. Nat Rev Gastroenterol Hepatol 7: 629–641.
    [Google Scholar]
  47. Yamaoka Y. , Kodama T. , Kashima K. , Graham D. Y. , Sepulveda A. R. . ( 1998;). Variants of the 3′ region of the cagA gene in Helicobacter pylori isolates from patients with different H. pylori-associated diseases. J Clin Microbiol 36: 2258–2263.
    [Google Scholar]
  48. Yamaoka Y. , El-Zimaity H. M. , Gutierrez O. , Figura N. , Kim J. G. , Kodama T. , Kashima K. , Graham D. Y. . ( 1999;). Relationship between the cagA 3′ repeat region of Helicobacter pylori, gastric histology, and susceptibility to low pH. Gastroenterology 117: 342–349 [CrossRef] [PubMed].
    [Google Scholar]
  49. Yamaoka Y. , Orito E. , Mizokami M. , Gutierrez O. , Saitou N. , Kodama T. , Osato M. S. , Kim J. G. , Ramirez F. C. , other authors . ( 2002;). Helicobacter pylori in North and South America before Columbus. FEBS Lett 517: 180–184 [CrossRef] [PubMed].
    [Google Scholar]
  50. Yula E. , Nagiyev T. , Kaya O. A. , İnci M. , Celik M. M. , Köksal F. . ( 2013;). Detection of primary clarithromycin resistance of Helicobacter pylori and association between cagA + status and clinical outcome. Folia Microbiol (Praha) 58: 141–146 [CrossRef] [PubMed].
    [Google Scholar]
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