Association of circulating VacA-neutralizing antibodies with gastric cancer and duodenal ulcer.

ABSTRACT

OBJECTIVE: To study the association between anti-VacA antibodies and pre-neoplastic lesions (IM), gastric cancer (GC), and duodenal ulcer (DU). METHODS: A case-control study that included 347 patients, 90 with IM, 60 with GC, 52 with DU, and 145 with non-atrophic gastritis was conducted. For the analysis, a polytomous logistic regression models were used. Anti-VacA antibodies were identified in sera from these patients, either by Western blot assay (WB), using antigens produced by H. pylori s1m1 strain, or by neutralization assay challenging HeLa cells with H. pylori VacA s1m1 cytotoxin. RESULTS: Results of the WB assay showed no association between WB-anti-VacA antibodies and gastroduodenal diseases. In contrast, when antibodies that neutralize VacA cytotoxic activity were studied, a significant association was found with IM (OR 2.7, 95% CI 1.4-5.1) and DU (OR 2.3, 95% CI 1.1-4.9) and an even stronger association with GC (OR 3.9, 95% CI 1.8-8.5). A significant association with histological subtypes of GC (diffuse and intestinal) and of IM (complete and incomplete) was also found. In addition, the association showed a significant dose-response effect in the case of GC, but not of DU or IM. These associations did not change substantially after adjustment for confounding factors. MAIN CONCLUSION: This study showed that VacA-neutralizing antibodies are significantly associated with gastroduodenal diseases, especially GC, and that they might be used as risk markers of GC and DU.