None have used immunoblot assays, excluded cases diagnosed within the first few years after sample collection, or covered multiple diverse areas. In mainland China, where approximately half of all global gastric cancer cases currently occur, only four prospective studies have examined the associations of H pylori infection with gastric cancer. In the aforementioned pooled analysis by HCCG (n=274 CGC cases) and a subsequent meta-analysis of 34 studies that also included many retrospective studies, H pylori infection showed either a null or negative association with CGC in populations in Europe, the USA, and Australia, but a positive, albeit more modest compared with NCGC, association in east Asian populations. Previous studies of H pylori infection and cardia gastric cancer (CGC), which accounts for approximately 30% of gastric cancer, have produced conflicting findings, especially between studies in east Asia and Europe, the USA, and Australia. More recently, in a pooled analysis of three nested case-control studies of populations in Europe, the USA, and Australia using a more sensitive immunoblot assay (HelicoBlot 2♱) for H pylori infection, the reported RR was 17♰ (11♶–25♰ n=189 cases) for NCGC, much higher than that obtained using ELISA in the same study population. In a pooled analysis undertaken by the Helicobacter and Cancer Collaborative Group that included 12 prospective studies, H pylori infection as established by ELISA was associated with a 3♰-fold (95% CI 2♳–3♸ n=762 cases) increased risk of NCGC, with a higher RR (5♹, 95% CI 3♴–10♳ n=223 cases) after restricting analyses to cases with blood samples collected over 10 years before cancer diagnosis. For non-cardia gastric cancer (NCGC), most studies have consistently shown a positive association with H pylori infection, but the relative risk (RR) estimates varied by more than 20 times, partly because of differences in study design, assay methods used, and exclusion criteria applied to reduce the effects of gastric atrophy on H pylori seropositivity. Overall, we identified six pooled analyses or meta-analyses that included approximately 20 prospective studies and a larger number of retrospective studies, with approximately a third involving east Asian populations. pylori” or “ Helicobacter pylori”) and (“gastric” or “non-cardia” or “cardia” or “stomach”) and (“cancer” or “carcinoma”) and (“risk” or “association”) were used. We searched for articles in PubMed published in English, Chinese, and other languages (including Japanese and Korean with English abstracts available, but with a focus on papers published in English) from Jan 1, 1990, to Dec 8, 2020, for individual studies or pooled or meta-analyses on Helicobacter pylori infection and risks of gastric cancer. The Lancet Regional Health – Western Pacific.The Lancet Regional Health – Southeast Asia.The Lancet Gastroenterology & Hepatology.

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