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Helicobacter pylori infection may increase the risk of both histotypes of gastric carcinoma (GC): intestinal (IGC) and diffuse (DGC). Polymorphism of the main H. pylori virulence factors, cagA and vacA, could have a different impact on the histological variety of GC.Two hundred and twenty-six H. pylori colonies were examined from 28 GC patients: 15 with IGC and 13 with DGC. DNA was extracted from bacteria and a PCR was performed using primers specific for cagA, the 3′ cagA variable region and s and m regions of vacA.There were 214 cagA+ strains and 55.61% of them were isolated from IGC cases; there were 12 cagA− colonies and they were all isolated from DGC (P<0.001). Most patients were infected by strains with more than one cagA structural type. No strains with a particular cagA type were found to be significantly more frequent in either histological variety of GC. A percentage of 43.90 of strains with vacA subtype s1/m1 were isolated from IGC, whereas 80.95% of vacA subtype s1/m2 strains were isolated from DGC cases (P<0.001).Polymorphism of the main virulence genes of H. pylori may play different roles in the pathogenesis of IGC and DGC.