Exposure to Commonly Used Drugs and the Risk of Gastric Cancer: An Umbrella Review of Meta-Analyses

SIMPLE SUMMARY: To date, several systematic reviews and meta-analyses have explored associations between commonly used drugs and gastric cancer (GC) risk, with inconsistent conclusions on relationships and methodological quality. No attempts have been made to quantify the credibility of these findings. Hence, it is necessary to compare the results of individual reviews by looking into existing systematic reviews and meta-analyses, providing an overview of the findings of a particular association. This is the first umbrella review to evaluate the validity and credibility of evidence from previously published systematic reviews and meta-analyses on observational studies and to identify associations between commonly used drugs and GC risk and its subtypes. ABSTRACT: Recently, attention has been paid to some medications and gastric cancer (GC) risk. This review aimed to evaluate associations between commonly used drugs and GC risk and to grade evidence from published systematic reviews and meta-analyses. This umbrella review was registered in PROSPERO (CRD42022320276). The systematic reviews and meta-analyses of observational studies were retrieved by searching Embase, PubMed, and Web of Science. The evidence strength of commonly used drugs and GC risk was categorized into four grades: weak, suggestive, highly suggestive, and strong. Of 19 associations between commonly used drugs and GC risk and its subtypes, none was supported by convincing or highly suggestive evidence. The risk of GC related to non-steroidal anti-inflammatory drugs (NSAIDs), non-aspirin NSAIDs, and acid-suppressive drugs, as well as the risk of non-cardia GC related to NSAIDs and aspirin, was supported by suggestive evidence. The results showed that a reduced GC risk was associated with two drug types (NSAIDs and non-aspirin NSAIDs), and an increased GC risk was associated with acid-suppressing drugs at the suggestive evidence level. Moreover, NSAIDs and aspirin reduced non-cardia GC risk as supported by suggestive evidence. However, the evidence supporting statins or metformin in reducing GC risk was weak, and thus future studies are required to clarify these associations.