• Huiqin Gao, Lunan Li, Ke Geng, Changzheng Teng, Yuanyuan Chen, Fei Chu, and Yi Zhao.
• Department of Gastroenterology, Guoyang County People's Hospital, Guoyang Branch of Anhui Provincial Hospital, Guoyang, Anhui, China.
• Medicine (Baltimore). 2022 Dec 9; 101 (49): e32228e32228.

BackgroundThis study aimed to systematically analyze the association between long-term use of proton pump inhibitors (PPIs) and the risk of gastric cancer (GC).MethodsWe performed a systematic search of articles on the relationship between long-term use of PPIs and the risk of GC from PubMed and EMBASE. We calculated the pooled odds ratio of GC in PPI users compared to non-PPI users using random-effects models.ResultsThis meta-analysis included 18 studies from 20 different databases with 4348,905 patients enrolled. In the random effects model, we found that an increased risk of GC among PPI users (OR = 1.94; 95% CI [1.43, 2.64]). The long-term use of PPIs compared with histamine-2 receptor antagonist users did not increase the risk of GC (OR = 1.65; 95% CI [0.92, 2.97]). Stratified analysis showed that PPI users had a significantly increased risk of noncardia GC (OR = 2.53; 95% CI [2.03, 3.15]), but had a relatively small relationship with the risk of gastric cardia cancer. (OR = 1.79; 95% CI [1.06, 3.03]). With the extension of PPI use time, the estimated risk value decreases (<1 year: OR = 6.33, 95% CI [3.76, 10.65]; 1-3 years: OR = 1.82, 95% CI [1.30, 2.55]; >3 years: OR = 1.25, 95% CI [1.00, 1.56]). Despite Helicobacter pylori eradication, the long-term use of PPIs did not alter the increased risk of GC (OR = 2.29; 95% CI [1.57, 3.33]).ConclusionOur meta-analysis found that PPI use may be associated with an increased risk of GC. Further research on the causal relationship between these factors is necessary.Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.

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