Vacuolating cytotoxin genotypes are strong markers of gastric cancer and duodenal ulcer-associated Helicobacter pylori strains: a matched case-control study.

The Helicobacter pylori virulence gene, cagA, and active forms of the vacuolating cytotoxin gene, vacA, are major determinants of pathogenesis. However, previous studies linking these factors to disease risk have often included patients using aspirin/nonsteroidal anti-inflammatory agents (NSAIDs) or acid-suppressing drugs, both of which may confound results. Also, particularly for gastric cancer (GC), controls have often been of quite different ages. Here, we performed a careful study in a "clean" Belgian population with gastric cancer cases age and sex matched to 4 controls and with a parallel duodenal ulcer (DU) group. As in other populations, there was a close association between the presence of cagA and the vacA s1 genotype. For GC, associations were found for vacA s1-positive (P = 0.01, odds ratio [OR], 9.37; 95% confidence interval [CI], 1.16 to 201.89), i1-positive (P = 0.003; OR, 12.08; 95% CI, 1.50 to 259.64), and cagA-positive status (P < 0.05; OR, infinity; 95% CI, 0.76 to infinity). For DU, associations were found with vacA s1 (P = 0.002; OR, 6.04; 95% CI, 1.52 to 27.87) and i1 (P = 0.004; OR, 4.35; 95% CI, 1.36 to 14.78) status but not with cagA status. Neither condition showed independent associations with the vacA m1 allele or with more biologically active forms of cagA with longer 3' variable regions. In this Belgian population, the best markers of gastric cancer- and duodenal ulcer-associated strains are the vacA s1 and i1 genotypes. This fits with experimental data showing that the s and i regions are the key determinants of vacuolating cytotoxin activity.