Multiple Repeats of Helicobacter pylori CagA C-Terminal Motifs Predict the Risk of Gastric Cancer in Iran

CagA, a 120- to 145-kD Helicobacter pylori (H. pylori) protein, increases the risk of atrophic gastritis and gastric cancer (GC). The pathogenic CagA contains a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the C-terminal portion of the protein. The aim of this study was to determine the number and type of EPIYA (glutamine–proline–isoleucine–tyrosine–alanine) motifs within the cagA 3' variable region among H. pylori isolates and their association with GC. The total number of 206 individuals (170 controls and 36 patients with GC) referring to the endoscopy units of several cities in Iran (2008-2014) were recruited. The polymerase chain reaction (PCR) amplification was performed to determine the presence of H. pylori, cagA gene, and EPIYA motifs. In this study, 81 (47.6%) and 22 (61.1%) of the controls and patients with GC were carriers of cagA+ strains, respectively. The overall frequency of EPIYA-AB, EPIYA-ABC, EPIYA-ABCC, and EPIYA-ABCCC in patients with GC were 0%, 59%, 9%, and 31.8%, respectively. The results of regression analysis showed a significant association between EPIYA-ABCCC motif and the risk of GC [OR = 9.99 (95%CI: 2.17-45.88), p = 0.003]. We propose that patients infected with H. pylori strains harboring more than one CagA EPIYA C motif (EPIYA-ABCCC) have an increased risk of GC, thus, testing for this genotype may have clinical usefulness.