Proton Pump Inhibitors and Cancer Risk: A Comprehensive Review of Epidemiological and Mechanistic Evidence
<b>Background:</b> Proton pump inhibitors (PPIs) are commonly prescribed long-acting drugs used to treat acid reflux, gastroesophageal reflux disease (GERD), and peptic ulcers. Recently, concerns have been raised about their safety, particularly due to the association between long-term P...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-03-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/13/7/1970 |
| _version_ | 1797212373219540992 |
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| author | Ibrahim O. Sawaid Abraham O. Samson |
| author_facet | Ibrahim O. Sawaid Abraham O. Samson |
| author_sort | Ibrahim O. Sawaid |
| collection | DOAJ |
| description | <b>Background:</b> Proton pump inhibitors (PPIs) are commonly prescribed long-acting drugs used to treat acid reflux, gastroesophageal reflux disease (GERD), and peptic ulcers. Recently, concerns have been raised about their safety, particularly due to the association between long-term PPI use and cancer development. Multiple comprehensive studies have consistently suggested a noteworthy link between prolonged PPI usage and an increased risk of developing gastric, esophageal, colorectal, and pancreatic cancers, yet the precise underlying mechanism remains elusive. <b>Methods:</b> First, we review the extensive body of research that investigates the intricate relationship between cancer and PPIs. Then, we predict PPI toxicity using the prodrug structures with the ProTox-II webserver. Finally, we predict the relative risk of cancer for each PPI, using PubMed citation counts of each drug and keywords related to cancer. <b>Results:</b> Our review indicates that prolonged PPI use (exceeding three months) is significantly associated with an elevated risk of cancer, while shorter-term usage (less than three months) appears to pose a comparatively lower risk. Our review encompasses various proposed mechanisms, such as pH and microbiome alterations, vitamin and mineral malabsorption, hypergastrinemia, and enterochromaffin-like cell proliferation, while ProTox-II also suggests aryl hydrocarbon receptor binding. Potentially, the PubMed citations count suggests that the PPIs omeprazole and lansoprazole are more associated with cancer than pantoprazole and esomeprazole. In comparison, the H2R blocker, famotidine, is potentially less associated with cancer than PPIs, and may serve as a safer alternative treatment for periods beyond 3 months. <b>Conclusions:</b> Despite the well-established cancer risk associated with PPIs, it is notable that these medications continue to be widely prescribed for periods longer than 3 months. Thus, it is of paramount importance for clinicians and patients to thoughtfully evaluate the potential risks and benefits of long-term PPI usage and explore alternative treatments before making informed decisions regarding their medical management. |
| first_indexed | 2024-04-24T10:41:21Z |
| format | Article |
| id | doaj.art-87bd9d8b35fd432191ddfb37c8c028ac |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-04-24T10:41:21Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-87bd9d8b35fd432191ddfb37c8c028ac2024-04-12T13:21:11ZengMDPI AGJournal of Clinical Medicine2077-03832024-03-01137197010.3390/jcm13071970Proton Pump Inhibitors and Cancer Risk: A Comprehensive Review of Epidemiological and Mechanistic EvidenceIbrahim O. Sawaid0Abraham O. Samson1Azrieli Faculty of Medicine, Bar Ilan University, Safed 1311502, IsraelAzrieli Faculty of Medicine, Bar Ilan University, Safed 1311502, Israel<b>Background:</b> Proton pump inhibitors (PPIs) are commonly prescribed long-acting drugs used to treat acid reflux, gastroesophageal reflux disease (GERD), and peptic ulcers. Recently, concerns have been raised about their safety, particularly due to the association between long-term PPI use and cancer development. Multiple comprehensive studies have consistently suggested a noteworthy link between prolonged PPI usage and an increased risk of developing gastric, esophageal, colorectal, and pancreatic cancers, yet the precise underlying mechanism remains elusive. <b>Methods:</b> First, we review the extensive body of research that investigates the intricate relationship between cancer and PPIs. Then, we predict PPI toxicity using the prodrug structures with the ProTox-II webserver. Finally, we predict the relative risk of cancer for each PPI, using PubMed citation counts of each drug and keywords related to cancer. <b>Results:</b> Our review indicates that prolonged PPI use (exceeding three months) is significantly associated with an elevated risk of cancer, while shorter-term usage (less than three months) appears to pose a comparatively lower risk. Our review encompasses various proposed mechanisms, such as pH and microbiome alterations, vitamin and mineral malabsorption, hypergastrinemia, and enterochromaffin-like cell proliferation, while ProTox-II also suggests aryl hydrocarbon receptor binding. Potentially, the PubMed citations count suggests that the PPIs omeprazole and lansoprazole are more associated with cancer than pantoprazole and esomeprazole. In comparison, the H2R blocker, famotidine, is potentially less associated with cancer than PPIs, and may serve as a safer alternative treatment for periods beyond 3 months. <b>Conclusions:</b> Despite the well-established cancer risk associated with PPIs, it is notable that these medications continue to be widely prescribed for periods longer than 3 months. Thus, it is of paramount importance for clinicians and patients to thoughtfully evaluate the potential risks and benefits of long-term PPI usage and explore alternative treatments before making informed decisions regarding their medical management.https://www.mdpi.com/2077-0383/13/7/1970CCKB2R—cholecystokinin B2 receptorECL cells—enterochromaffin-like cellsGERD—gastroesophageal reflux diseaseGI—gastrointestinalH2R—histamine H2 receptorH2RB—H2R blocker |
| spellingShingle | Ibrahim O. Sawaid Abraham O. Samson Proton Pump Inhibitors and Cancer Risk: A Comprehensive Review of Epidemiological and Mechanistic Evidence Journal of Clinical Medicine CCKB2R—cholecystokinin B2 receptor ECL cells—enterochromaffin-like cells GERD—gastroesophageal reflux disease GI—gastrointestinal H2R—histamine H2 receptor H2RB—H2R blocker |
| title | Proton Pump Inhibitors and Cancer Risk: A Comprehensive Review of Epidemiological and Mechanistic Evidence |
| title_full | Proton Pump Inhibitors and Cancer Risk: A Comprehensive Review of Epidemiological and Mechanistic Evidence |
| title_fullStr | Proton Pump Inhibitors and Cancer Risk: A Comprehensive Review of Epidemiological and Mechanistic Evidence |
| title_full_unstemmed | Proton Pump Inhibitors and Cancer Risk: A Comprehensive Review of Epidemiological and Mechanistic Evidence |
| title_short | Proton Pump Inhibitors and Cancer Risk: A Comprehensive Review of Epidemiological and Mechanistic Evidence |
| title_sort | proton pump inhibitors and cancer risk a comprehensive review of epidemiological and mechanistic evidence |
| topic | CCKB2R—cholecystokinin B2 receptor ECL cells—enterochromaffin-like cells GERD—gastroesophageal reflux disease GI—gastrointestinal H2R—histamine H2 receptor H2RB—H2R blocker |
| url | https://www.mdpi.com/2077-0383/13/7/1970 |
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