The role of autoimmune gastritis in gastric cancer risk: a systematic review and meta-analysis

Autoimmune gastritis (AIG) is a chronic, progressive condition characterized by immune-mediated attack on gastric parietal cells, predominantly in the corpus and fundus of the stomach. This process leads to mucosal atrophy, which is a key precursor lesion in the established Correa cascade of gastric carcinogenesis. While AIG has long been considered a precursor to gastric cancer (GC), the exact magnitude of this risk and the independent role of AIG remain debated. The primary purpose of this systematic review and meta-analysis was to evaluate the precise relationship between AIG and the risk of gastric cancer. We performed a comprehensive search of relevant databases and included studies that assessed GC risk in patients diagnosed with AIG. The data were synthesized using random-effects models to calculate pooled hazard ratios (HRs). Studies were stratified based on H. pylori infection status and histological confirmation of AIG. Risk of bias was evaluated using the Cochrane risk-of-bias tool. The meta-analysis included 8 studies with a total of 10 cohorts. The pooled HR for GC risk in patients with AIG was 1.93 (95% CI: 1.59–2.33). H. pylori-negative AIG patients exhibited a significantly higher risk (HR = 4.31) compared to those with H. pylori-positive AIG (HR = 2.36). Histologically confirmed AIG was associated with an increased risk of GC, with a pooled HR of 4.82 (95% CI: 2.44–9.51). Subgroup analysis of studies diagnosing AIG histologically showed no heterogeneity (I² = 0%). The overall heterogeneity across all studies was substantial, with an I² of 77%. Our findings suggest that AIG may be a potential independent risk factor for GC particularly in H. pylori-negative patients and those with histologically confirmed AIG. These results highlight the importance of considering histological diagnosis and H. pylori status in clinical surveillance. Autoimmune gastritis (AIG) is an independent risk factor for gastric cancer (GC), with a pooled HR of 1.93. Risk stratification is essential, as the risk is highest in H.pylori-negative AIG patients (HR = 4.31) and those with histologically confirmed AIG (HR = 4.82). The strong association in the H.pylori-negative subgroup necessitates rigorous endoscopic surveillance (every 3-5 years), as the absence of infection does not guarantee a low risk. Future clinical guidelines should prioritize systematic histological evaluation over serological markers alone for risk assessment in AIG patients.