Investigation of Association between oipA and iceA1/iceA2 Genotypes of Helicobacter pylori and Gastric Cancer in Iran

  • Aghdam, Saeed Mahboubi (Department of Biology, Pardis International, Guilan University) ;
  • Sardari, Zeinab (Department of Biology, Pardis International, Guilan University) ;
  • Safaralizadeh, Reza (Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz) ;
  • Bonyadi, Mortaza (Center of Excellence for Biodiversity, Faculty of Natural Sciences, University of Tabriz) ;
  • Abdolmohammadi, Reza (Legal Medicine Research Center, Legal Medicine Organization) ;
  • Moghadam, Mostafa Soltani (Department of Biology, Pardis International, Guilan University) ;
  • Khalilnezhad, Ahad (Department of Immunology, Medical School, Shahid Beheshti University of Medical Sciences)
  • Published : 2014.10.23


Background: H pylori is the main causative agent of Gastric cancer and chronic gastritis. Genetic diversity of H. pylori has major contribution in its pathogenesis. We investigated the prevalence of oipA and iceA1/iceA2 positive strains of H. pylori among patients with gastric cancer and gastritis. Materials and Methods: Sampling performed by means of endoscopy from 86 patients. DNA was extracted from tissue samples using DNA extraction kit. PCR assay was performed and products were monitored by Agarose Gel Electrophoresis. Results: Urease Test and 16S rRNA PCR did not show significant differences in detection of H. pylori. The frequency of iceA1 allele in patients with gastric cancer was significantly higher than those with gastritis (p<0.05). However, there was no significant difference in prevalence of oipA and iceA2 genes among the two groups of patients (p>0.05). Conclusions: The iceA1 gene, but the oipA and iceA2 genes, is associated with H. pylori-induced gastric cancer. However, confirmatory studies must be performed in future.


Chronic gastritis;gastric cancer;genetic diversity;Helicobacter pylori


  1. Basiri Z, Safaralizadeh R, Bonyadi MJ, et al (2014). Helicobacter pylori vacA d1 genotype predicts risk of gastric adenocarcinoma and peptic ulcers in northwestern Iran. Asian Pac J Cancer Prev, 15, 1575-79.
  2. Alm RA, Bina J, Andrews BM, et al (2000). Comparative genomics of Helicobacter pylori: analysis of the outer membrane protein families. Infect Immun, 68, 4155-68.
  3. Ben Mansour K, Fendri C, Zribi M, et al (2010). Prevalence of Helicobacter pylori vacA, cagA, iceA and oipA genotypes in Tunisian patients. Ann Clin Microbiol Antimicrob, 9, 10.
  4. Chomvarin C, Namwat W, Chaicumpar K, et al (2008). Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA and babA2 genotypes in Thai dyspeptic patients. Int J Infect Dis, 12, 30-6.
  5. Ciftci IH, Uslan I, Dilek FH, et al (2011). Investigation of Helicobacter pylori iceA1 and iceA2 genes in patients with chronic gastritis and gastric cancer. Mikrobiyol Bul, 45, 228-33 (in Russian).
  6. Correa P (2013). Gastric cancer: overview. Gastroenterol Clin North Am, 42, 211-7.
  7. Dabiri H, Maleknejad P, Yamaoka Y, et al (2009). Distribution of Helicobacter pylori cagA, cagE, oipA and vacA in different major ethnic groups in Tehran, Iran. J Gastroenterol Hepatol, 24, 1380-6.
  8. de Martel C, Forman D, Plummer M (2013). Gastric cancer: epidemiology and risk factors. Gastroenterol Clin North Am, 42, 219-40.
  9. Graham DY, Yamaoka Y (1998). H. pylori and cagA: relationships with gastric cancer, duodenal ulcer, and reflux esophagitis and its complications. Helicobacter, 3, 145-51.
  10. Dossumbekova A, Prinz C, Mages J, et al (2006). Helicobacter pylori HopH (OipA) and bacterial pathogenicity: genetic and functional genomic analysis of hopH gene polymorphisms. J Infect Dis, 194, 1346-55.
  11. Go MF, Kapur V, Graham DY, et al (1996). Population genetic analysis of Helicobacter pylori by multilocus enzyme electrophoresis: extensive allelic diversity and recombinational population structure. J Bacteriol, 178, 3934-8.
  12. Gonzalez CA, Figueiredo C, Lic CB, et al (2011). Helicobacter pylori cagA and vacA genotypes as predictors of progression of gastric preneoplastic lesions: a long-term follow-up in a high-risk area in Spain. Am J Gastroenterol, 106, 867-74.
  13. Ilver D, Arnqvist A, Ogren J, et al (1998). Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. Science, 279, 373-7.
  14. Kim SY, Woo CW, Lee YM, et al (2001). Genotyping CagA, VacA subtype, IceA1, and BabA of Helicobacter pylori isolates from Korean patients, and their association with gastroduodenal diseases. J Korean Med Sci, 16, 579-84.
  15. Konturek JW (2003). Discovery by Jaworski of Helicobacter pylori and its pathogenetic role in peptic ulcer, gastritis and gastric cancer. J Physiol Pharmacol, 54, 23-41.
  16. Kudo T, Lu H, Wu JY, et al (2007). Pattern of transcription factor activation in Helicobacter pylori-infected Mongolian gerbils. Gastroenterology, 132, 1024-38.
  17. Kusters JG, van Vliet AH, Kuipers EJ (2006). Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev, 19, 449-90.
  18. Marshall BJ (2001). One Hundred Years of Discovery and Rediscovery of Helicobacter pylori and Its Association with Peptic Ulcer Disease.
  19. Lage AP, Godfroid E, Fauconnier A, et al (1995). Diagnosis of Helicobacter pylori infection by PCR: comparison with other invasive techniques and detection of cagA gene in gastric biopsy specimens. J Clin Microbiol, 33, 2752-6.
  20. Liu YE, Gong YH, Sun LP, (2012). The relationship between H. pylori virulence genotypes and gastric diseases. Pol J Microbiol, 61, 147-50.
  21. Markovska R, Boyanova L, Yordanov D, et al (2011). Helicobacter pylori oipA genetic diversity and its associations with both disease and cagA, vacA s, m, and i alleles among Bulgarian patients. Diagn Microbiol Infect Dis, 71, 335-40.
  22. Marshall DG, Coleman DC, Sullivan DJ, et al (1996). Genomic DNA fingerprinting of clinical isolates of Helicobacter pylori using short oligonucleotide probes containing repetitive sequences. J Appl Bacteriol, 81, 509-17.
  23. Martins LC, Corvelo TC, Demachki S, et al (2005). Clinical and pathological importance of vacA allele heterogeneity and cagA status in peptic ulcer disease in patients from North Brazil. Mem Inst Oswaldo Cruz, 100, 875-81.
  24. Naumann M (2005). Pathogenicity island-dependent effects of Helicobacter pylori on intracellular signal transduction in epithelial cells. Int J Med Microbiol, 295, 335-41.
  25. Peek RM, van Doorn LJ, Donahue JP, et al (1999). Helicobacter pylori iceA is transcribed in vivo and iceA1 expression is associated with enhanced mucosal inflammation. Gastroenterology, 116, 279.
  26. Peek RM, Jr., Thompson SA, Donahue JP, et al (1998). Adherence to gastric epithelial cells induces expression of a Helicobacter pylori gene, iceA, that is associated with clinical outcome. Proc Assoc Am Physicians, 110, 531-44.
  27. van Doorn LJ, Figueiredo C, Sanna R, et al (1998). Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori. Gastroenterology, 115, 58-66.
  28. Rothenbacher D, Brenner H (2003). Burden of Helicobacter pylori and H. pylori-related diseases in developed countries: recent developments and future implications. Microbes Infect, 5, 693-703.
  29. Salih BA, Abasiyanik MF, Ahmed N (2007). A preliminary study on the genetic profile of cag pathogenicity-island and other virulent gene loci of Helicobacter pylori strains from Turkey. Infect Genet Evol, 7, 509-12.
  30. Thomazini C, Pinheiro N, Pardini M, et al (2006). Helicobacter pylori and gastric cancer: distribution of cagA and vacA genotypes in patients with gastric carcinoma. Brasileiro de Patologia e Medicina Laboratorial, 42, 25-30.
  31. Vega AE, Cortinas TI, Puig ON, et al (2010). Molecular characterization and susceptibility testing of Helicobacter pylori strains isolated in western Argentina. Int J Infect Dis, 14, 85-92.
  32. Westbrook JI, Duggan AE, Duggan JM, et al (2005). A 9 year prospective cohort study of endoscoped patients with upper gastrointestinal symptoms. Eur J Epidemiol, 20, 619-27.
  33. Wroblewski LE, Peek RM, Jr. (2013). Helicobacter pylori in gastric carcinogenesis: mechanisms. Gastroenterol Clin North Am, 42, 285-98.
  34. Yamaoka Y, Kwon DH, Graham DY (2000). A M(r) 34,000 proinflammatory outer membrane protein (oipA) of Helicobacter pylori. Proc Natl Acad Sci U S A, 97, 7533-8.
  35. Yamaoka Y, Kikuchi S, el-Zimaity HM, et al (2002). Importance of Helicobacter pylori oipA in clinical presentation, gastric inflammation, and mucosal interleukin 8 production. Gastroenterology, 123, 414-24.
  36. Zhang YW, Eom SY, Yim DH, et al (2013). Evaluation of the relationship between dietary factors, CagA-positive Helicobacter pylori infection, and RUNX3 promoter hypermethylation in gastric cancer tissue. World J Gastroenterol, 19, 1778-87.

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