Helicobacter pylori cagA, vacA, and iceA genotypes and clinical outcomes: a cross-sectional study in central Vietnam

Helicobacter pylori is the most common cause of gastroduodenal diseases. The concept that cagA-positive H. pylori is a risk factor for gastric cancer appears to be true only for H. pylori strains from Western countries. Other virulent genes may have a synergistic interaction with cagA during pathogenesis. This study aims to investigate H. pylori cagA, vacA, and iceA prevalence, genotypes, and their association to clinical outcomes in Vietnamese patients. The cagA status and vacA and iceA genotypes were determined using the PCR technique on DNA extracted from gastric biopsies of 141 patients with gastroduodenal diseases. After performing molecular analysis for cagA, vacA, and iceA genes, samples with mixed H. pylori strains, positivity, or negativity for both cagA and cagPAI-empty site, or unidentified genotypes were excluded. Finally, 107 samples were examined. The presence of the cagA, vacA, and iceA genes were detected in 77.6%, 100%, and 80.4% of cases, respectively. Notably, cagA( +) with EPIYA-ABD, vacA s1i1m1, vacA s1i1m2, iceA1, and iceA2 accounted for 73.8%, 44.9%, 33.6%, 48.6%, and 31.8% of cases, respectively. Four iceA2 subtypes (24-aa, 59-aa, 94-aa, and 129-aa variants) were found, with the 59-aa variant the most prevalent (70.6%). The cagA( +)/vacAs1i1m1/iceA1 and cagA( +)/vacAs1i1m2/iceA1 combinations were found in 26.2% and 25.1% of cases, respectively. A multivariable logistic regression analysis was performed, after adjusting for age and gender, with the gastritis group was used as a reference control. Statistically significant associations were found between the vacA s1i1m2 genotype, the iceA1 variant, and the cagA( +)/vacAs1i1m2/iceA1 combination and gastric cancer; the adjusted ORs were estimated as 18.02 (95% CI: 3.39-95.81), 4.09 (95% CI: 1.1-15.08), and 16.19 (95% CI: 3.42-76.66), respectively. Interestingly, for the first time, our study found that vacA s1i1m2, but not vacA s1i1m1, was a risk factor for gastric cancer. This study illustrates the genetic diversity of the H. pylori cagA, vacA, and iceA genes across geographical regions and contributes to understanding the importance of these genotypes for clinical outcomes.