Helicobacter pylori virulence factors and host interleukin (IL) polymorphisms are implicated in the pathogenesis of gastric adenocarcinoma (GCA), but have not been investigated together, in the South African context of low GCA incidence and high H pylori prevalence. Aims: To determine, based on these factors, the potential for developing GCA in a local cohort with H pylori-associated dyspepsia. Methods: Seventy-nine patients underwent gastroscopy and biopsy. Helicobacter pylori-positive

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... were analysed for virulence factors; cytotoxin-associated antigen (CagA) and vacuolating toxin (VacA) and mosaics (Vac A m1/m2, Vac A s1/s2 or combinations). Host DNA was analysed for targeted regions in IL-1B and IL-1RN genes, to determine polymorphisms of IL-1B-511*T and IL-1RN (variable number tandem repeat [VNTR]). Results: The mean age was 43 years (SD ±11.7), 66% were female. Forty-eight patients (60%) were H pylori positive, 50% (24/48) demonstrated a virulent organism and 42% (20/48) of these demonstrated the most virulent carcinogenic combination; VacA m1/s1 and CagA. IL-1RN VNTR was sequenced in 25 specimens and IL-1B511 polymorphisms in 48 patients; the high-risk IL-1B511 TT allele was present in 52% (25/48) and TC allele in 33% (16/48). Overall, 85% (41/48) of patients demonstrated high-risk genetic polymorphisms. The highest risk associated with GCA, a combination of H pylori VacAm1/s1 virulence factor and IL-1B511 TT or TC allele, was demonstrated in 42% (20/48). Conclusion: Almost half the patients have a combination of virulent H pylori and carcinogenic IL polymorphism. The implication of these observations on the risk of developing GCA requires further elucidation.