Tehran University of Medical Sciences Journal of Medical Bacteriology 2251-8649 13 4 2025 12 12 75 83 Haniyeh Bashi Zadeh Fakhar Department of Human Geneticse, Science And Research Branch, Branch, Islamic Azad University, Tehran, Iran Sara Taheri Neyestanaki Department of Cell and Molecular, Science and Research Branch, Islamic Azad University, Tehran, Iran Melika Jalalian 1. Cancer Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran 2. Department of Cell and Molecular Biology, TeMS.C, Islamic Azad University, Tehran, Iran Parnian Sadat Shahidi 1. Cancer Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran 2. Department of Cell and Molecular Biology, TeMS.C, Islamic Azad University, Tehran, Iran Hassan Rasouli Moulan Department of Cell and Molecular Biology, TeMS.C, Islamic Azad University, Tehran, Iran 2025 08 30 2025 10 26 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. https://jmb.tums.ac.ir/index.php/jmb/article/view/614