- BACKGROUND & AIMS: Reports in the literature regarding the relationship of infection with cagA -positive strains of Helicobacter pylori to gastric cancer over and above H. pylori infection alone are conflicting. The aim of this study was to estimate the magnitude of the risk for gastric cancer associated with cagA seropositivity and to identify any sources of heterogeneity between studies. METHODS: A meta-analysis of case-control studies with age- and sex-matched controls, which provided raw data on the infection rates with H. pylori and cagA strains of H. pylori as detected by serology or polymerase chain reaction DNA, was performed. RESULTS: A comprehensive literature search identified 16 qualified studies with 2284 cases and 2770 controls. H. pylori and cagA seropositivity significantly increased the risk for gastric cancer by 2.28- and 2.87-fold, respectively. Among H. pylori -infected populations, infection with cagA -positive strains further increased the risk for gastric cancer by 1.64-fold (95% confidence interval [CI], 1.21-2.24) overall and by 2.01-fold (95% CI, 1.21-3.32) for noncardiac gastric cancer. Gastric cancer at the cardia is not associated with H. pylori infection or cagA -positive strains of H. pylori. Patient age and site of gastric cancer contributed to the heterogeneity between studies. CONCLUSIONS: Infection with cagA -positive strains of H. pylori increases the risk for gastric cancer over the risk associated with H. pylori infection alone. Searching for cagA status over H. pylori infection may confer additional benefit in identifying populations at greater risk for gastric cancer.