Association Between CagA-Positive Helicobacter pylori Strains and Clinical Outcomes inPatients with Gastritis, Peptic Ulcer, and Gastric Cancer: A Cross-Sectional Study
-
Haniyeh Bashi Zadeh Fakhar
,
Sara Taheri Neyestanaki
,
Melika Jalalian
,
Parnian Sadat Shahidi
,
Hassan Rasouli Moulan
Abstract
Background: Helicobacter pylori infection, particularly with cagA-positive strains, is strongly associated with severe gastrointestinal outcomes such as peptic ulcer and gastric cancer, though the strength of this association varies across populations. This study investigates the link between cagA positivity and clinical diagnoses in Iranian patients to evaluate its potential as a predictor of disease severity in a high-prevalence region.
Methods: This cross-sectional study included 125 patients with gastrointestinal symptoms, of whom 36 H. pylori-positive individuals were analyzed for cagA status using PCR on gastric biopsy specimens. The association between cagA positivity and clinical diagnoses (gastritis, peptic ulcer, gastric cancer) was assessed using chi-square and logistic regression analyses in SPSS v26.
Results: Of 36 H. pylori-positive patients, 63.89% were infected with cagA-positive strains. A significant association was found between cagA positivity and disease severity, with higher prevalence in peptic ulcer (78.3%) and gastric cancer (80.0%) compared to chronic gastritis (42.9%) (p < 0.05).
Conclusion: cagA-positive H. pylori strains are significantly associated with peptic ulcer and gastric cancer, highlighting their role in disease severity. cagA detection may serve as a valuable biomarker for risk stratification and targeted management in high-prevalence regions.
1. Park SK. Extra-digestive Manifestations of Helicobacter pylori Infection – An Overview. Extradigestive Manifestations of Helicobacter Pylori Infection - An Overview. InTech; 2016.
2. Kunovsky L, Dite P, Jabandziev P, et al. Helicobacter pylori infection and other bacteria in pancreatic cancer and autoimmune pancreatitis. World J Gastro Onco 2021; 13(8):835.
3. Wongcha-Um A, Thongkongthun T, Vilaichone RK, et al. Helicobacter pylori: pathogenesis, clinical impact, and modern treatment approaches. In: Helicobacter pylori - Causes, Symptoms, and Treatment Options. IntechOpen; 2025.
4. Sukthaworn S, Moungthard H, Sirisai C, et al. Helicobacter pylori cytotoxin-associated gene a (cagA) and vacuolating cytotoxin gene a (vacA) genotypes in gastrointestinal patients from central Thailand. Cureus 2024; 16(7):e64164.
5. Yi M, Chen S, Yi X, et al. Helicobacter pylori infection process: from the molecular world to clinical treatment. Front Microbiol 2025; 16:1541140.
6. Yang JC, Wang TH, Wang HJ, et al. Genetic analysis of the cytotoxin-associated gene and the vacuolating toxin gene in Helicobacter pylori strains isolated from Taiwanese patients. Am J Gastroenterol 1997; 92(8):1316-21.
7. Hedayati MA, Khani D. Relationship of social risk factors and Helicobacter pylori infection with pathological characteristics of gastric carcinoma. Iran J Med Microbiol 2020; 20(14):1.
8. Esteghamati A, Sayyahfar S, Khanaliha K, et al. Prevalence and clinical relevance of cagA and pipA genotypes of Helicobacter pylori in children and adults with gastrointestinal diseases in Tehran, Iran. Med J Islam Repub Iran 2023; 37:125-132.
9. Taravat A, Bashi Zadeh Fakhar H, Shaghai B, et al. Evaluation of serum levels of anti-Helicobacter pylori IgG and IgA by ELISA method in patients with gastric ulcer in Chalous, Iran. J Med Bacteriol 2023; 12(1):
10. Naing C, Aung HH, Aye SN, et al. CagA toxin and risk of Helicobacter pylori-infected gastric phenotype: A meta-analysis of observational studies. PLosOne 2024; 19(8):e0307172.
11. Basso D, Zambon CF, Letley DP, et al. Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms. Gastroenterol 2008; 135(1):91-9.
12. Azuma T, Yamazaki S, Yamakawa A, et al. Association between diversity in the Src homology 2 domain--containing tyrosine phosphatase binding site of Helicobacter pylori CagA protein and gastric atrophy and cancer. J Infect Dis 2004; 189(5):820-7.
13. Shiota S, Watada M, Matsunari O, et al. Helicobacter pylori iceA, clinical outcomes, and correlation with cagA: a meta-analysis. PLosOne 2012; 7(1):e30354.
14. Wattanawongdon W, Simawaranon Bartpho T, Tongtawee T. Relationship between Helicobacter pylori virulence genes and gastroduodenal disease. J Int Med Res 2023; 51(3):3000605231161465.
15. Ali M, Khan AA, Tiwari SK, et al. Association between cag-pathogenicity island in Helicobacter pylori isolates from peptic ulcer, gastric carcinoma, and non-ulcer dyspepsia subjects with histological changes. World J Gastroenterol 2005; 11(43):6815-22.
16. Nomura AM, Pérez-Pérez GI, Lee J, et al. Relation between Helicobacter pylori cagA status and risk of peptic ulcer disease. Am J Epidemiol 2002; 155(11):1054-9.
17. Valmaseda Pérez T, Gisbert JP, Pajares García JM. Geographic differences and the role of cagA gene in gastroduodenal diseases associated with Helicobacter pylori infection. Rev Esp Enferm Dig 2001; 93(7):471-80.
18. Amieva MR, Vogelmann R, Covacci A, et al. Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science 2003; 300(5624):1430-4.
19. Ayala G, Escobedo-Hinojosa WI, de la Cruz-Herrera CF, et al. Exploring alternative treatments for Helicobacter pylori infection. World J Gastroenterol 2014; 20(6):1450-69.
20. Atherton JC, Omar-El EM, Hale JL. Differences in CagA tyrosine phosphorylation motif influence H. pylori strains between East Asian and Western populations. J Med Microbiol 2008; 57(Pt 10):57-62.
21. Krashias G, Bashiardes S, Potamitou A, et al. Prevalence of Helicobacter pylori cagA and vacA genes in Cypriot patients. J Infect Dev Ctries 2012; 7(9):642-50.
22. Zhou J, Zhang J, Xu C, et al. cagA genotype and variants in Chinese Helicobacter pylori strains and relationship to gastroduodenal diseases. J Med Microbiol 2004; 53(Pt 3):231-5.
23. Gatti LL, Fagundes E, Souza EK, et al. cagA, vacA alleles and babA2 genotypes of Helicobacter pylori associated with gastric disease in Brazilian adult patients. Diagn Microbiol Infect Dis 2005; 51(4):231-5.
24. Bustos-Fraga S, Salinas-Pinta F, Vicuña-Almeida Y, et al. Prevalence of Helicobacter pylori genotypes: cagA, vacA, vacC, babA2, dupA, iceA1, oipA and their association with gastrointestinal diseases. BMC Gastroenterol 2023; 23(1):125-32.
25. Huang JQ, Zheng GF, Sumanac K, et al. Meta-analysis of the relationship between cagA seropositivity and gastric cancer. Gastroenterol 2003; 125(6):1636-44.
26. Kianmehr M, Zargar M, Hormati A, et al. Prevalence of Helicobacter pylori and its cagA gene in patients with gastric cancer or peptic ulcer at an Iranian medical center. Novel Biomed 2020; 9(1):24-7.
27. Pan ZJ, van der Hulst RW, Feller M, et al. Equally high prevalences of infection with cagA-positive Helicobacter pylori in Chinese patients with peptic ulcer disease and those with chronic gastritis-associated dyspepsia. J Clin Microbiol 1997; 35(6):1344-7.
28. Mansour-Ghanaei F, Yousefi M, Joukar F. Prevalence of Helicobacter pylori infection among children in Rasht, Northern Iran. MEJDD 2009; 1(2): 84-8.
29. Chen XJ, Yan J, Shen YF. Dominant cagA/vacA genotypes and coinfection frequency of H. pylori in peptic ulcer or chronic gastritis patients in Zhejiang province and correlation among different genotype coinfection and severity of the disease. Chin Med J 2005; 118(6):460-7.
30. Figueiredo C, Van Doorn LJ, Nogueira C, et al. Helicobacter pylori genotypes are associated with clinical outcome in Portuguese patients and show a high prevalence of infections with multiple strains. Scand J Gastroenterol 2001; 36(2):128-35.
31. Crabtree JE, Wyatt JI, Sobala GM, et al. Systemic and mucosal humoral responses to Helicobacter pylori in gastric cancer. Gut 1993; 34(10):1339-43.
32. Hedayati MA, Khani D. Relationship of social risk factors and Helicobacter pylori infection with pathological characteristics of gastric carcinoma. Iran J Med Microbiol 2020; 20(14):1.
33. Eshaghi F, Bashi Zadeh Fakhar H, Ghane M, et al. Diagnostic evaluation of Streptococcus gallolyticus infection in patients with colon diseases by polymerase chain reaction (PCR) and culturing methods. Int J Cancer Manag 2020; 13(6):e101903.
2. Kunovsky L, Dite P, Jabandziev P, et al. Helicobacter pylori infection and other bacteria in pancreatic cancer and autoimmune pancreatitis. World J Gastro Onco 2021; 13(8):835.
3. Wongcha-Um A, Thongkongthun T, Vilaichone RK, et al. Helicobacter pylori: pathogenesis, clinical impact, and modern treatment approaches. In: Helicobacter pylori - Causes, Symptoms, and Treatment Options. IntechOpen; 2025.
4. Sukthaworn S, Moungthard H, Sirisai C, et al. Helicobacter pylori cytotoxin-associated gene a (cagA) and vacuolating cytotoxin gene a (vacA) genotypes in gastrointestinal patients from central Thailand. Cureus 2024; 16(7):e64164.
5. Yi M, Chen S, Yi X, et al. Helicobacter pylori infection process: from the molecular world to clinical treatment. Front Microbiol 2025; 16:1541140.
6. Yang JC, Wang TH, Wang HJ, et al. Genetic analysis of the cytotoxin-associated gene and the vacuolating toxin gene in Helicobacter pylori strains isolated from Taiwanese patients. Am J Gastroenterol 1997; 92(8):1316-21.
7. Hedayati MA, Khani D. Relationship of social risk factors and Helicobacter pylori infection with pathological characteristics of gastric carcinoma. Iran J Med Microbiol 2020; 20(14):1.
8. Esteghamati A, Sayyahfar S, Khanaliha K, et al. Prevalence and clinical relevance of cagA and pipA genotypes of Helicobacter pylori in children and adults with gastrointestinal diseases in Tehran, Iran. Med J Islam Repub Iran 2023; 37:125-132.
9. Taravat A, Bashi Zadeh Fakhar H, Shaghai B, et al. Evaluation of serum levels of anti-Helicobacter pylori IgG and IgA by ELISA method in patients with gastric ulcer in Chalous, Iran. J Med Bacteriol 2023; 12(1):
10. Naing C, Aung HH, Aye SN, et al. CagA toxin and risk of Helicobacter pylori-infected gastric phenotype: A meta-analysis of observational studies. PLosOne 2024; 19(8):e0307172.
11. Basso D, Zambon CF, Letley DP, et al. Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms. Gastroenterol 2008; 135(1):91-9.
12. Azuma T, Yamazaki S, Yamakawa A, et al. Association between diversity in the Src homology 2 domain--containing tyrosine phosphatase binding site of Helicobacter pylori CagA protein and gastric atrophy and cancer. J Infect Dis 2004; 189(5):820-7.
13. Shiota S, Watada M, Matsunari O, et al. Helicobacter pylori iceA, clinical outcomes, and correlation with cagA: a meta-analysis. PLosOne 2012; 7(1):e30354.
14. Wattanawongdon W, Simawaranon Bartpho T, Tongtawee T. Relationship between Helicobacter pylori virulence genes and gastroduodenal disease. J Int Med Res 2023; 51(3):3000605231161465.
15. Ali M, Khan AA, Tiwari SK, et al. Association between cag-pathogenicity island in Helicobacter pylori isolates from peptic ulcer, gastric carcinoma, and non-ulcer dyspepsia subjects with histological changes. World J Gastroenterol 2005; 11(43):6815-22.
16. Nomura AM, Pérez-Pérez GI, Lee J, et al. Relation between Helicobacter pylori cagA status and risk of peptic ulcer disease. Am J Epidemiol 2002; 155(11):1054-9.
17. Valmaseda Pérez T, Gisbert JP, Pajares García JM. Geographic differences and the role of cagA gene in gastroduodenal diseases associated with Helicobacter pylori infection. Rev Esp Enferm Dig 2001; 93(7):471-80.
18. Amieva MR, Vogelmann R, Covacci A, et al. Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science 2003; 300(5624):1430-4.
19. Ayala G, Escobedo-Hinojosa WI, de la Cruz-Herrera CF, et al. Exploring alternative treatments for Helicobacter pylori infection. World J Gastroenterol 2014; 20(6):1450-69.
20. Atherton JC, Omar-El EM, Hale JL. Differences in CagA tyrosine phosphorylation motif influence H. pylori strains between East Asian and Western populations. J Med Microbiol 2008; 57(Pt 10):57-62.
21. Krashias G, Bashiardes S, Potamitou A, et al. Prevalence of Helicobacter pylori cagA and vacA genes in Cypriot patients. J Infect Dev Ctries 2012; 7(9):642-50.
22. Zhou J, Zhang J, Xu C, et al. cagA genotype and variants in Chinese Helicobacter pylori strains and relationship to gastroduodenal diseases. J Med Microbiol 2004; 53(Pt 3):231-5.
23. Gatti LL, Fagundes E, Souza EK, et al. cagA, vacA alleles and babA2 genotypes of Helicobacter pylori associated with gastric disease in Brazilian adult patients. Diagn Microbiol Infect Dis 2005; 51(4):231-5.
24. Bustos-Fraga S, Salinas-Pinta F, Vicuña-Almeida Y, et al. Prevalence of Helicobacter pylori genotypes: cagA, vacA, vacC, babA2, dupA, iceA1, oipA and their association with gastrointestinal diseases. BMC Gastroenterol 2023; 23(1):125-32.
25. Huang JQ, Zheng GF, Sumanac K, et al. Meta-analysis of the relationship between cagA seropositivity and gastric cancer. Gastroenterol 2003; 125(6):1636-44.
26. Kianmehr M, Zargar M, Hormati A, et al. Prevalence of Helicobacter pylori and its cagA gene in patients with gastric cancer or peptic ulcer at an Iranian medical center. Novel Biomed 2020; 9(1):24-7.
27. Pan ZJ, van der Hulst RW, Feller M, et al. Equally high prevalences of infection with cagA-positive Helicobacter pylori in Chinese patients with peptic ulcer disease and those with chronic gastritis-associated dyspepsia. J Clin Microbiol 1997; 35(6):1344-7.
28. Mansour-Ghanaei F, Yousefi M, Joukar F. Prevalence of Helicobacter pylori infection among children in Rasht, Northern Iran. MEJDD 2009; 1(2): 84-8.
29. Chen XJ, Yan J, Shen YF. Dominant cagA/vacA genotypes and coinfection frequency of H. pylori in peptic ulcer or chronic gastritis patients in Zhejiang province and correlation among different genotype coinfection and severity of the disease. Chin Med J 2005; 118(6):460-7.
30. Figueiredo C, Van Doorn LJ, Nogueira C, et al. Helicobacter pylori genotypes are associated with clinical outcome in Portuguese patients and show a high prevalence of infections with multiple strains. Scand J Gastroenterol 2001; 36(2):128-35.
31. Crabtree JE, Wyatt JI, Sobala GM, et al. Systemic and mucosal humoral responses to Helicobacter pylori in gastric cancer. Gut 1993; 34(10):1339-43.
32. Hedayati MA, Khani D. Relationship of social risk factors and Helicobacter pylori infection with pathological characteristics of gastric carcinoma. Iran J Med Microbiol 2020; 20(14):1.
33. Eshaghi F, Bashi Zadeh Fakhar H, Ghane M, et al. Diagnostic evaluation of Streptococcus gallolyticus infection in patients with colon diseases by polymerase chain reaction (PCR) and culturing methods. Int J Cancer Manag 2020; 13(6):e101903.
| Issue | Vol 13 No 4 (2025) | |
| Section | Original Articles | |
| Keywords | ||
| CagA-Positive Clinical outcomes Gastric Cancer Helicobacter pylori Peptic ulcer. | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Bashi Zadeh Fakhar H, Taheri Neyestanaki S, Jalalian M, Shahidi PS, Rasouli Moulan H. Association Between CagA-Positive Helicobacter pylori Strains and Clinical Outcomes inPatients with Gastritis, Peptic Ulcer, and Gastric Cancer: A Cross-Sectional Study. J Med Bacteriol. 2025;13(4):75-83.
