Associations between colonization with Helicobacter pylori and risk of gastrointestinal tract cancers: An umbrella review of meta-analyses

Abstract

Background: Several studies have investigated the association between Helicobacter pylori colonization and gastrointestinal malignancies. However, inconsistent results have been found, leaving no clear consensus. Materials and Methods: Umbrella review of meta-analyses of observational studies aiming to understand the association between Helicobacter pylori colonization and gastrointestinal cancers in humans. MEDLINE, the Cochrane Library of Systematic Reviews, EMBASE, Scopus and Google Scholar were searched from their inception to January 2025. Quality assessment was performed with the AMSTAR 2 tool. The study was registered on PROSPERO (CRD42024523832). Results: Of 1320 records, 38 meta-analyses were included, investigating biliary tract, colorectal, oesophageal, gastric, liver and pancreatic cancers. After dealing with primary study overlap and updating meta-analyses with over 160 studies, Helicobacter pylori was positively associated with biliary tract [OR 2.67 (1.57–4.52)], colorectal [OR 1.40 (1.23–1.60)], gastric [OR 2.10 (1.34–3.31)], liver [OR 5.13 (3.14–8.38)] and pancreatic [OR 1.24 (1.04–1.48)] cancers, while oesophageal adenocarcinoma (EAC) was inversely associated with it [OR.58 (.46–.72)]. The cytotoxic-associated gene A (CagA) protein was positively associated with biliary [OR 2.19 (1.07–4.50)], colorectal [OR 2.04 (1.47–2.82)], oesophageal squamous cell carcinoma [OR 1.56 (1.30–1.89)] and gastric cancers [OR 2.53 (1.94–3.30)], and inversely associated with EAC [OR.60 (.44–.81)] and pancreatic [OR.85 (.75–.97)] cancers. Our results sprout from mostly critically low-quality meta-analyses and moderate to high quality primary studies. Conclusion: Exposure to Helicobacter pylori colonization and its proteins is associated with not only gastric cancer, but also other GI tract cancers. Directionally different results may be seen when specific virulence factors/organ sites are investigated.