Skip to content
1887

Abstract

infection is a major cause of peptic ulcer and gastric adenocarcinoma. The infection progression to severe diseases depends on several factors, including bacterial ones. CagA and VacA are two major virulence factors widely studied and implicated in diseases.

Although the allelic prevalence of the s, m, i and d regions of the gene and their relation with gastric disease outcomes have been largely studied, there is a gap in knowledge regarding the prevalence and the association of the c region with those pathologies. This polymorphic region could exhibit a large variability which might impact the virulence of the bacterium and the severity of gastric damage.

The aim of this study was to investigate the prevalence of c alleles and to assess the association of mosaicism with gastric damage in a large Moroccan population.

positive gastric biopsies, obtained in 709 consenting patients who consulted the gastroenterology department of the Hassan II University Hospital of Fez (Morocco) for clinical endoscopy, between 2009 and 2019, were used in this study. DNA extracted from the biopsy samples was used to determine the c genotype using specific PCRs. , s, m, d and i genotypes of these samples were previously determined.

The c2 genotype was detected in 44.7% of samples and the c1 genotype in 16.5% of cases. Multiple infections (detection of the two c allelic forms) were obtained in 9% of samples. Correlation of c genotype with pathologies showed that the c1 allele was strongly associated with the risk of gastric cancer (GC) [odds ratio=3.14, confidence intervals 95% (1.08–9.09)].

The results of this study confirm that despite the large genetic diversity, the genotypic distribution is marked by a predominance of the less virulent strains in Morocco. Also, even if allelic combinations seem to impact the toxicity of this bacterium, patients infected with c1 genotype are more likely to develop GC than those infected by c2 genotype.

Funding
This study was supported by the:
  • Centre Hospitalier Universitaire Hassan II de Fès (Award PR04-12 13)
    • Principal Award Recipient: NotApplicable
  • Centre National pour la Recherche Scientifique et Technique (Award 03P/2016)
    • Principal Award Recipient: NotApplicable
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001969
2025-03-07
2026-02-16

Metrics

Loading full text...

Full text loading...

/deliver/fulltext/jmm/74/3/jmm001969.html?itemId=/content/journal/jmm/10.1099/jmm.0.001969&mimeType=html&fmt=ahah

References

  1. de Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health 2020; 8:e180–e190 [View Article] [PubMed]
    [Google Scholar]
  2. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71:209–249 [View Article] [PubMed]
    [Google Scholar]
  3. Letley DP, Atherton JC. Natural diversity in the N terminus of the mature vacuolating cytotoxin of Helicobacter pylori determines cytotoxin activity. J Bacteriol 2000; 182:3278–3280 [View Article] [PubMed]
    [Google Scholar]
  4. Ji X, Fernandez T, Burroni D, Pagliaccia C, Atherton JC et al. Cell specificity of Helicobacter pylori cytotoxin is determined by a short region in the polymorphic midregion. Infect Immun 2000; 68:3754–3757 [View Article] [PubMed]
    [Google Scholar]
  5. Chung C, Olivares A, Torres E, Yilmaz O, Cohen H et al. Diversity of VacA intermediate region among Helicobacter pylori strains from several regions of the world. J Clin Microbiol 2010; 48:690–696 [View Article] [PubMed]
    [Google Scholar]
  6. Rhead JL, Letley DP, Mohammadi M, Hussein N, Mohagheghi MA et al. A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer. Gastroenterol 2007; 133:926–936 [View Article] [PubMed]
    [Google Scholar]
  7. Hussein NR, Mohammadi M, Talebkhan Y, Doraghi M, Letley DP et al. Differences in virulence markers between Helicobacter pylori strains from Iraq and those from Iran: potential importance of regional differences in H. pylori-associated disease. J Clin Microbiol 2008; 46:1774–1779 [View Article] [PubMed]
    [Google Scholar]
  8. Basso D, Zambon C, Letley DP, Stranges A, Marchet A et al. Clinical Relevance of Helicobacter pylori cagA and vacA Gene Polymorphisms. Gastroenterol 2008; 135:91–99 [View Article] [PubMed]
    [Google Scholar]
  9. Ogiwara H, Sugimoto M, Ohno T, Vilaichone R-K, Mahachai V et al. Role of deletion located between the intermediate and middle regions of the Helicobacter pylori vacA gene in cases of gastroduodenal diseases. J Clin Microbiol 2009; 47:3493–3500 [View Article] [PubMed]
    [Google Scholar]
  10. Soyfoo DM, Doomah YH, Xu D, Zhang C, Sang H-M et al. New genotypes of Helicobacter pylori VacA d-region identified from global strains. BMC Mol Cell Biol 2021; 22:4 [View Article] [PubMed]
    [Google Scholar]
  11. Bakhti SZ, Latifi-Navid S, Mohammadi S, Zahri S, Bakhti FS et al. Relevance of Helicobacter pylori vaca 3’-end region polymorphism to gastric cancer. Helicobacter 2016; 21:305–316 [View Article] [PubMed]
    [Google Scholar]
  12. Boukhris SA, Benajah DA, Rhazi K, Ibrahimi SA, Nejjari C et al. Prevalence and distribution of Helicobacter pylori cagA and vacA genotypes in the moroccan population with gastric disease. Eur J Clin Microbiol Infect Dis 2012; 31:1775–1781 [View Article]
    [Google Scholar]
  13. Sambrook J, Russel DW. Molecular Cloning A Laboratory Manual Cold Spring Harbor Laboratory Press (CSHL Press); 2001
    [Google Scholar]
  14. Resnick RM, Cornelissen MT, Wright DK, Eichinger GH, Fox HS et al. Detection and typing of human papillomavirus in archival cervical cancer specimens by DNA amplification with consensus primers. J Natl Cancer Inst 1990; 82:1477–1484 [View Article] [PubMed]
    [Google Scholar]
  15. El Khadir M, Alaoui Boukhris S, Benajah D-A, El Rhazi K, Ibrahimi SA et al. VacA and CagA status as biomarker of two opposite end outcomes of Helicobacter pylori infection (gastric cancer and duodenal ulcer) in a moroccan population. PLoS One 2017; 12:e0170616 [View Article] [PubMed]
    [Google Scholar]
  16. El Khadir M, Boukhris SA, Zahir SO, Benajah D-A, Ibrahimi SA et al. CagE, cagA and cagA 3’ region polymorphism of Helicobacter pylori and their association with the intra-gastric diseases in Moroccan population. Diagn Microbiol Infect Dis 2021; 100:115372 [View Article] [PubMed]
    [Google Scholar]
  17. Robinwarren J, Marshall B. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1983; 321:1273–1275 [View Article]
    [Google Scholar]
  18. Salvatori S et al. Helicobacter pylori and gastric cancer: pathogenetic mechanisms. Int J Mol Sci 2023; 24:2895 [View Article]
    [Google Scholar]
  19. El Khadir M, Boukhris Alaoui S, Benajah D-A, Ibrahimi SA, Chbani L et al. VacA genotypes and cagA-EPIYA-C motifs of Helicobacter pylori and gastric histopathological lesions. Int J Cancer 2020; 147:3206–3214 [View Article] [PubMed]
    [Google Scholar]
  20. Rudi J, Kolb C, Maiwald M, Kuck D, Sieg A et al. Diversity of Helicobacter pylori vacA and cagA genes and relationship to VacA and CagA protein expression, cytotoxin production, and associated diseases. J Clin Microbiol 1998; 36:944–948 [View Article] [PubMed]
    [Google Scholar]
  21. Bakhti SZ, Latifi-Navid S, Zahri S. Unique constellations of five polymorphic sites of Helicobacter pylori vacA and cagA status associated with risk of gastric cancer. Infect Genet Evol 2020; 79:104167 [View Article] [PubMed]
    [Google Scholar]
  22. Bakhti SZ, Gholizadeh S et al. Helicobacter pylori vaca c1 genotype is a benefit biomarker for prediction of gastric cancer risk in ardabil. Int Clin Neurosci J 2016; 3:164–169 [View Article]
    [Google Scholar]
  23. Aftab H, Miftahussurur M, Subsomwong P, Ahmed F, Khan AKA et al. Two populations of less-virulent Helicobacter pylori genotypes in Bangladesh. PLoS One 2017; 12:e0182947 [View Article] [PubMed]
    [Google Scholar]
  24. Mandour S, Abdelmohsen A, Medhat M, Abdeltawab D, Elfarash A et al. Virulence profile of helicobacter pylori detected in gastric biopsies of patients undergoing endoscopy in upper Egypt. Bull Pharm Sci 2021; 44:213–224 [View Article]
    [Google Scholar]
  25. Subsomwong P, Miftahussurur M, Uchida T, Vilaichone R-K, Ratanachu-Ek T et al. Prevalence, risk factors, and virulence genes of Helicobacter pylori among dyspeptic patients in two different gastric cancer risk regions of Thailand. PLoS One 2017; 12:e0187113 [View Article] [PubMed]
    [Google Scholar]
  26. Ubukata H, Nagata H, Tabuchi T, Konishi S, Kasuga T et al. Why is the coexistence of gastric cancer and duodenal ulcer rare? examination of factors related to both gastric cancer and duodenal ulcer. Gastric Cancer 2011; 14:4–12 [View Article] [PubMed]
    [Google Scholar]
  27. Hawkey CJ, Wilson I, Naesdal J, Långström G, Swannell AJ et al. Influence of sex and Helicobacter pylori on development and healing of gastroduodenal lesions in non-steroidal anti-inflammatory drug users. Gut 2002; 51:344–350 [View Article] [PubMed]
    [Google Scholar]
  28. Wu H-C, Tuo B-G, Wu W-M, Gao Y, Xu Q-Q et al. Prevalence of peptic ulcer in dyspeptic patients and the influence of age, sex, and Helicobacter pylori infection. Dig Dis Sci 2008; 53:2650–2656 [View Article] [PubMed]
    [Google Scholar]
  29. Chen TS, Chang FY, Lee SD. Smoking and male gender rather than CagA protein are associated with increased risk for duodenal ulcer in Helicobacter pylori-infected patients in Taiwan. Dig Dis Sci 1999; 44:2076–2080 [View Article] [PubMed]
    [Google Scholar]
  30. Korman MG, Hansky J, Eaves ER, Schmidt GT. Influence of cigarette smoking on healing and relapse in duodenal ulcer disease. Gastroenterol 1983; 85:871–874 [PubMed]
    [Google Scholar]
  31. Rosenstock S, Jørgensen T, Bonnevie O, Andersen L. Risk factors for peptic ulcer disease: a population based prospective cohort study comprising 2416 danish adults. Gut 2003; 52:186–193 [View Article] [PubMed]
    [Google Scholar]
  32. Tuo B, Wen G, Wei J, Liu X, Wang X et al. Estrogen regulation of duodenal bicarbonate secretion and sex-specific protection of human duodenum. Gastroenterol 2011; 141:854–863 [View Article] [PubMed]
    [Google Scholar]
  33. Trang TTH, Binh TT, Yamaoka Y. Relationship between vacA types and development of gastroduodenal diseases. Toxins 2016; 8:182 [View Article] [PubMed]
    [Google Scholar]
  34. Sheikh AF, Yadyad MJ, Goodarzi H, Hashemi SJ, Aslani S et al. CagA and vacA allelic combination of Helicobacter pylori in gastroduodenal disorders. Microb Pathog 2018; 122:144–150 [View Article] [PubMed]
    [Google Scholar]
/content/journal/jmm/10.1099/jmm.0.001969
Loading
/content/journal/jmm/10.1099/jmm.0.001969
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An error occurred
Approval was partially successful, following selected items could not be processed due to error