Abstract
Background: A recently developed multiplex serology method has been used to identify new virulence factors of Helicobacter pylori. The results of associations with gastric cancer have not been consistent across studies, possibly due to differences in the studied populations and/or the genetic diversity of H. pylori. We aimed to investigate the association between seropositivity to fifteen different H. pylori antigens using the multiplex serology method and the risk of gastric cardia (GCA) and gastric non-cardia (GNCA) adenocarcinomas in northeastern Iran, where the population has both a high prevalence of H. pylori infection and a high incidence of gastric adenocarcinoma. Methods: We included 272 cases of gastric adenocarcinoma (142 GCA, 103 GNCA, and 22 unspecified tumors) and 524 controls who were individually matched to cases for age, sex, and place of residence in this populationbased case-control study. Seropositivity to H. pylori was assessed using both multiplex serology and H. pylori IgG ELISA (BioHit, Finland). Results: H. pylori positivity based on the whole-cell ELISA test and also multiplex serology assay; defined as recognizing antibodies to ≥ 4 antigens; were not significantly associated with any of study groups; and its positivity rate was generally lower in ELISA assay than multiplex serology; GCA cases (79.6% vs. 95.1%), GNCA cases (74.8% vs. 95.2%), and controls (82.4% vs. 94.7%). Of the 15 antibodies in the multiplex assay, 10 showed no significant association with all gastric adenocarcinoma, GCA, or GNCA; while CagA and VacA were associated with a significantly increased risk of these cancers in multivariate adjusted models. Conversely, GroEL and NapA were significantly associated with a reduced risk of all gastric adenocarcinoma and GNCA. Conclusion: Our study showed no association between ELISA test positivity and gastric cancer risk, which implies that this method should not be used for risk stratification and referral for H. pylori eradication. Rather, effective risk stratification would require further characterization of H. pylori strain exposure with virulence factors such as CagA and VacA antigens. Our finding regarding lower risk of gastric adenocarcinoma among GroEL and NapA antigen positive subjects deserves additional investigation.
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