Long Term Proton Pump Inhibitor Use and Risk of Stomach Cancer: An Umbrella Review with Updated Evidence through 2025

Proton pump inhibitors are frequently prescribed to treat acid related disorders and there have been shortcomings that the use of proton pump inhibitors may affect long term safety especially the risk of stomach cancer. Conflicting reports of observational studies have also been published and confusion abides as a result of confounding by indication and reverse causation. Purpose: To determine the relationship between the risk of the occurrence of stomach cancer and the long term use of proton pump inhibitors in a large population based cohort study on the basis of stringent adjustment and sensitivity analyses. Methodology: A retrospective cohort study was an investigation utilizing linked healthcare and cancer registry data. The inclusion criteria included adults who had a two-years baseline and were classified as non users, short term users, or, long term users that were one or more years of use. Within a period of twelve months, previous prescription before diagnosis was eliminated to reduce the reverse causation. On multivariable Cox proportional hazards adjusted the population variables of metabolic conditions, Helicobacter pylori, and other comorbidities. Findings: 1,475 incidence gastric cancer cases were found in 328, 030 subjects who were followed up a median of 8.2 years. Whereas crude incidence was higher in long term users, adjusted analyses did not demonstrate any statistically significant association. There was no dose response relationship seen in increasing quartiles of cumulative exposure. Long lag period sensitivity analyses yielded similar null results. Conclusion: Long term proton pump inhibitor use was not directly linked with an increase in stomach cancer excessively adjusted and corrected after handling bias. It is still suggested that judicious prescribing and frequent re-evaluation should be done.