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Background: Increasingly, studies have focused on the relationship between Helicobacter pylori (H pylori) cytotoxin associated gene A protein (CagA) Glu-Pro-Ile-Tyr-Ala (EPIYA)-D motifs or multiple EPIYA-C phosphorylation sites and peptic ulcer disease (PUD) or gastric cancer (GC) risk. However, the conclusions have been inconsistent. The aim of this meta-analysis was to evaluate whether 1 CagA EPIYA-D motif or multiple EPIYA-C phosphorylation sites were associated with PUD or GC risk. Materials and methods: A literature search was performed in PubMed, Web of Science, Wanfang Data, Excerpt Medica Database, and the Chinese National Knowledge Infrastructure database to identify eligible research. We analyzed the odds ratios (OR) and 95% confidence intervals (CI) to assess the strength of association. Results: Compared with 1 EPIYA-C motif in Asian populations, 1 EPIYA-D site was associated with an increased GC risk (OR=1.91, 95% CI=1.19–3.07, P = .008). However, 1 EPIYA-D motif was not significantly associated with PUD (OR = 0.90, 95% CI = 0.46–1.76, P = .764), gastric ulcer (GU) (OR = 0.85, 95% CI = 0.27–2.63, P = .771), or duodenal ulcer (DU) (OR = 0.89, 95% CI = 0.25–3.16, P = .859) risk. Compared with no more than 1 EPIYA-C motif, multiple motifs were associated with increased PUD (OR = 2.33, 95% CI = 1.29–4.20, P = .005) and DU (OR = 2.32, 95% CI = 1.08–5.00, P = .031) risk in Asia and GC risk in the United States and Europe (OR = 3.28, 95% CI = 2.32–4.64, P < .001). Multiple EPIYA-C sites were not associated with GU risk (OR = 4.54, 95% CI = 0.95–21.83, P = .059). There was no publication bias identified in these comparisons. Conclusions: In Asia, 1 EPIYA-D motif was significantly associated with increased GC risk. Multiple EPIYA-C motifs were associated with increased PUD and DU risk, particularly in Asia. In the United States and Europe, multiple EPIYA-C motifs were associated with increased GC risk. Therefore, detection of polymorphic CagA EPIYA motifs may improve clinical prediction of disease risk.

Association of CagA EPIYA-D or EPIYA-C phosphorylation sites with peptic ulcer and gastric cancer risks