Inverse association of Helicobacter pylori cagPAI genotypes with risk of cardia and non‐cardia gastric adenocarcinoma

Iran is a high‐risk country for cardia gastric adenocarcinoma (CGA) in Central Asia, with an incidence rate five times the average global rate, and shows a high infection rate for Helicobacter pylori (69%). The aim was to examine the associations of multiple H. pylori cagPAI genotypes (ie cagH, cagL, cagG, and orf17) with the risk of CGA, non‐CGA, and different histological types of GA in Iran. A large number of H. pylori strains (N = 336) were successfully cultured and genotyped. Histopathological evaluations were performed. The analysis showed an inverse association between the cagH(+) genotype and the risk of CGA and intestinal‐type gastric adenocarcinoma (IGA) (adjusted ORs; 0.312 and 0.283, respectively), where the controls were nontumors. The orf17 (+) genotype decreased the risk of non‐CGA and diffuse‐type gastric adenocarcinoma (DGA)(adjusted ORs; 0.310 and 0.356, respectively). When the controls were those with nonatrophic gastritis, the cagG (+) genotype was negatively associated with the risk of CGA, non‐CGA, IGA, and DGA (adjusted ORs; 0.324, 0.366, 0.306, and 0.303, respectively). We did not find such a significant association for the cagL(+) genotype in multiple logistic regression analysis. Combination of the vacA c2 and cagPAI genotypes further decreased the risk estimates for GAs. This study showed the reverse association of H. pylori cagPAI genotypes—cagH (+) and cagG (+)—with the risk of CGA in male patients aged ≥ 55 in Iran. Presence of the vacA c2 genotype in combination with cagPAI genotypes showed strong inverse associations with the risk of CGA and non‐CGA. These findings may reveal a coordinated relationship between the vacA c2 and cagPAI genotypes.