Acid suppressive drugs and gastric cancer: A meta-analysis of observational studies

Ahn, Jeong Soo

doi:10.3748/wjg.v19.i16.2560

Cited by 109Helicobacter pylori-related gastroenterology studiesGastroesophageal reflux and treatmentsInflammatory mediators and NSAID effects

Acid suppressive drugs and gastric cancer: A meta-analysis of observational studies

Open access

Ahn, Jeong Soo·2013·World Journal of Gastroenterology

DOI 10.3748/wjg.v19.i16.2560PMC PMC3646149

Open this paper in CoChat — free account

Abstract

AIM: To evaluate the association between acid suppressive drug use and the development of gastric cancer. METHODS: A systematic search of relevant studies that were published through June 2012 was conducted using the MEDLINE (PubMed), EMBASE, and Cochrane Library databases. The search included observational studies on the use of histamine 2-receptor antagonists (H₂RAs) or proton pump inhibitors and the associated risk of gastric cancer, which was measured using the adjusted odds ratio (OR) or the relative risk and 95%CI. An independent extraction was performed by two of the authors, and a consensus was reached. RESULTS: Of 4595 screened articles, 11 observational studies (n = 94558) with 5980 gastric cancer patients were included in the final analyses. When all the studies were pooled, acid suppressive drug use was associated with an increased risk of gastric cancer risk (adjusted OR = 1.42; 95%CI: 1.29-1.56, I² = 48.9%, P = 0.034). The overall risk of gastric cancer increased among H₂RA users (adjusted OR = 1.40; 95%CI: 1.24-1.59, I² = 59.5%, P = 0.008) and PPI users (adjusted OR = 1.39; 95%CI: 1.19-1.64, I² = 0.0%, P = 0.377). CONCLUSION: Acid suppressive drugs are associated with an increased risk of gastric cancer. Further studies are needed to test the effect of acid suppressive drugs on gastric cancer.

Integrity signals

Registry

Crossref · 10.3748/wjg.v19.i16.2560

Cites

75 of 75 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Some studies and meta-analyses report an increased risk of developing GC in long-term PPI users up to 2.4 times greater, even after H. pylori eradication.
“with some studies and meta-analyses reporting an increased risk of developing GC in long-term PPI users[62,63] up to 2.4 times greater, even after Helicobacter pylori (H. pylori) eradication, according to a recent study[64]”
From Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified (2019) · cites this paper as [62]

Measuring inconsistency in meta-analyses
Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003) · BMJ · doi:10.1136/bmj.327.7414.557 · Cited by 63,139 · see citing works
Meta-analysis in clinical trials
DerSimonian, R., & Laird, N. (1986) · Controlled Clinical Trials · doi:10.1016/0197-2456(86)90046-2 · Cited by 39,552 · see citing works
Quantifying heterogeneity in a meta‐analysis
Higgins, J. P. T., & Thompson, S. G. (2002) · Statistics in Medicine · doi:10.1002/sim.1186 · Cited by 36,763 · see citing works
Meta-analysis of Observational Studies in Epidemiology<SUBTITLE>A Proposal for Reporting</SUBTITLE>
Stroup, D. F. (2000) · JAMA · doi:10.1001/jama.283.15.2008 · Cited by 20,623 · see citing works
Untitled work
(2014) · Medical Entomology and Zoology · Cited by 17,633 · see citing works
Statistical Aspects of the Analysis of Data From Retrospective Studies of Disease
(1959) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/22.4.719 · Cited by 14,689 · see citing works
ON ESTIMATING THE RELATION BETWEEN BLOOD GROUP AND DISEASE
Woolf, B. (1955) · Annals of Human Genetics · doi:10.1111/j.1469-1809.1955.tb01348.x · Cited by 2,739 · see citing works
A human model of gastric carcinogenesis.
Corréa, P. (1988) · PubMed · Cited by 1,433 · see citing works
Gastric cancer and Helicobacter pylori : a combined analysis of 12 case control studies nested within prospective cohorts
Helicobacter and Cancer Collaborative Group (2001) · Gut · doi:10.1136/gut.49.3.347 · Cited by 1,038 · see citing works
Atrophic Gastritis andHelicobacter pyloriInfection in Patients with Reflux Esophagitis Treated with Omeprazole or Fundoplication
Kuipers, E. J., Lundell, L. R., Klinkenberg–Knol, E. C., Havu, N., Festen, H. P. M., Liedman, B., Lamers, C. B. H. W., Jansen, J. B. �. �., Dalenbäck, J., Snel, P., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199604183341603 · Cited by 764 · see citing works
A Comparison of Five Maintenance Therapies for Reflux Esophagitis
Vigneri, S., Termini, R., Leandro, G., Badalamenti, S., Pantalena, M., Savarino, V., Mario, F. D., Battaglia, G., Mela, G. S., Pilotto, A., et al. (1995) · New England Journal of Medicine · doi:10.1056/nejm199510263331703 · Cited by 539 · see citing works
Long-term omeprazole treatment in resistant gastroesophageal reflux disease: Efficacy, safety, and influence on gastric mucosa
Klinkenberg–Knol, E. C., Nelis, F. G., Dent, J., Snel, P., Mitchell, B., Prichard, P. J., Lloyd, D., Havu, N., Frame, M. H., Román, J., et al. (2000) · Gastroenterology · doi:10.1016/s0016-5085(00)70135-1 · Cited by 533 · see citing works
Long-Term Treatment with Omeprazole for Refractory Reflux Esophagitis: Efficacy and Safety
Klinkenberg–Knol, E. C., Festen, H. P. M., Jansen, J. B. �. �., Lamers, C. B. H. W., Nelis, F., Snel, P., Luckers, A., Dekkers, C. P. M., Havu, N., & Meuwissen, S. G. M. (1994) · Annals of Internal Medicine · doi:10.7326/0003-4819-121-3-199408010-00001 · Cited by 422 · see citing works
Enterochromaffin-Like Cell Carcinoids of Gastric Mucosa in Rats after Life-Long Inhibition of Gastric Secretion
Havu, N. (2009) · Digestion · doi:10.1159/000199381 · Cited by 375 · see citing works
The Relation of Gastroesophageal Reflux Disease and Its Treatment to Adenocarcinomas of the Esophagus and Gastric Cardia
Chow, W.-H. (1995) · JAMA · doi:10.1001/jama.1995.03530060048032 · Cited by 365 · see citing works
Acid suppression: Optimizing therapy for gastroduodenal ulcer healing, gastroesophageal reflux disease, and stress-related erosive syndrome
Wolfe, M. M., & Sachs, G. M. (2000) · Gastroenterology · doi:10.1016/s0016-5085(00)70004-7 · Cited by 352 · see citing works
Gastrin and colorectal cancer: A prospective study
Thorburn*, C. M., Friedman‡, G. D., Dickinson§, C. J., Vogelman∥, J. H., Orentreich∥, N., & Parsonnet*, #. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70193-3 · Cited by 267 · see citing works
Increased risk of fundic gland polyps during long‐term proton pump inhibitor therapy
Jalving, M., Koornstra, J. J., Wesseling, J., Boezen, H. M., de Jong, S., & KLEIBEUKER, J. H. (2006) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2006.03127.x · Cited by 266 · see citing works
Review article: potential gastrointestinal effects of long‐term acid suppression with proton pump inhibitors
Laine, Ahnen, Mcclain, Solcia, & Walsh (2000) · Alimentary Pharmacology & Therapeutics · doi:10.1046/j.1365-2036.2000.00768.x · Cited by 247 · see citing works
GASTRIC CANCER IN PATIENTS WHO HAVE TAKEN CIMETIDINE
Mullen, P. W., & Guslandi, M. (1979) · The Lancet · doi:10.1016/s0140-6736(79)92040-3 · Cited by 243 · see citing works
Gastroesophageal reflux disease, use of H2 receptor antagonists, and risk of esophageal and gastric cancer
Farrow, D. C., Vaughan, T. L., Sweeney, C., Gammon, M. D., Chow, W. H., Risch, H. A., Stanford, J. L., Hansten, P. D., Mayne, S. T., Schoenberg, J. B., et al. (2000) · Cancer Causes & Control · doi:10.1023/a:1008913828105 · Cited by 228 · see citing works
Omeprazole versus H2-receptor antagonists in treating patients with peptic stricture and esophagitis
Marks, R. D., Richter, J. E., Rizzo, J. A., Koehler, R. E., Spenney, J. G., Mills, T. P., & Champion, G. (1994) · Gastroenterology · doi:10.1016/0016-5085(94)90749-8 · Cited by 216 · see citing works
Gastric mucosa during treatment with lansoprazole: Helicobacter pylori is a risk factor for argyrophil cell hyperplasia
Eissele, R., Brunner, G. H. G., Simon, B., Solcia, E., & Arnold, R. (1997) · Gastroenterology · doi:10.1053/gast.1997.v112.pm9041231 · Cited by 205 · see citing works
Gastric acid suppression and risk of oesophageal and gastric adenocarcinoma: a nested case control study in the UK
Rodríguez, L. A. G., Lagergren, J., & Lindblad, M. (2006) · Gut · doi:10.1136/gut.2005.086579 · Cited by 203 · see citing works
Proton pump inhibitors and risk of gastric cancer: a population-based cohort study
Poulsen, A. H., Christensen, S., McLaughlin, J. K., Thomsen, R. W., Sørensen, H. T., Olsen, J. H., & Friis, S. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6605024 · Cited by 158 · see citing works
Long-Term Omeprazole Treatment in Man: Effects on Gastric Endocrine Cell Populations
Lamberts, R., Creutzfeldt, W., Stöckmann, F., Jacubaschke, U., Maas, S., & Brunner, G. H. G. (2009) · Digestion · doi:10.1159/000199615 · Cited by 150 · see citing works
Who is using chronic acid suppression therapy and why?
Jacobson, B. C., Ferris, T. G. G., Shea, T. L., Mahlis, E. M., Lee, T. H.-Y., & Wang, T. C. (2003) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2003.07186.x · Cited by 143 · see citing works
Intragastric nitrites, nitrosamines, and bacterial overgrowth during cimetidine treatment.
Stockbrügger, R. W., Cotton, P. B., Eugenides, N., BARTHOLOMEW, B. A., Hill, M. J., & Walters, C. L. (1982) · Gut · doi:10.1136/gut.23.12.1048 · Cited by 135 · see citing works
Effect of Helicobacter pylori eradication on chronic gastritis during omeprazole therapy
Schenk, B. E., Kuipers, E. J., Nelis, G. F., Bloemena, E., Thijs, J. C., Snel, P., Luckers, A. E. G., Klinkenberg–Knol, E. C., Festen, H. P. M., Viergever, P. P., et al. (2000) · Gut · doi:10.1136/gut.46.5.615 · Cited by 130 · see citing works
Fundic gland polyps developing during omeprazole therapy.
El‐Zimaity, H. M. T., Jackson, F. W., & Graham, D. Y. (1997) · PubMed · Cited by 129 · see citing works
Changing Patterns of Helicobacter pylori Gastritis in Long‐Standing Acid Suppression
Moayyedi, P., Wason, C., Peacock, R., Walan, A., Bardhan, K. D., Axon, A. T. R., & Dixon, M. F. (2000) · Helicobacter · doi:10.1046/j.1523-5378.2000.00032.x · Cited by 122 · see citing works
Parietal cell protrusions and fundic gland cysts during omeprazole maintenance treatment
CATS, A., EDSCHENK, B., Bloemena, E., Roosendaal, R., LINDEMAN, J., Biemond, I., Klinkenberg–Knol, E. C., Meuwissen, S. G. M., & Kuipers, E. J. (2000) · Human Pathology · doi:10.1053/hupa.2000.7637 · Cited by 117 · see citing works
Elevated gastrin levels in patients with colon cancer or adenomatous polyps
Smith, J. P., Wood, J. G., & Solomon, T. E. (1989) · Digestive Diseases and Sciences · doi:10.1007/bf01536047 · Cited by 104 · see citing works
Bacterial overgrowth as a consequence of reduced gastric acidity
Stockbruegger, R. W. (1985) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365528509093749 · Cited by 97 · see citing works
Effects of Very Long (up to 10 Years) Proton Pump Blockade on Human Gastric Mucosa
Lamberts, R., Brunner, G., & Solcia, E. (2001) · Digestion · doi:10.1159/000048863 · Cited by 96 · see citing works
Drugs Five Years Later
Freston, J. W. (1982) · Annals of Internal Medicine · doi:10.7326/0003-4819-97-5-728 · Cited by 93 · see citing works
Gastric Endocrine Cells and Gastritis in Patients Receiving Long-Term Omeprazole Treatment
Solcia, E., Fiocca, R., Havu, N., Dalväg, A., & Carlsson, R. (2009) · Digestion · doi:10.1159/000200921 · Cited by 83 · see citing works
H2-receptor antagonists may increase the risk of cardio-oesophageal adenocarcinoma
Suleiman, U., Harrison, M., Britton, A. R., McPherson, K., & Bates, T. (2000) · European Journal of Cancer Prevention · doi:10.1097/00008469-200006000-00006 · Cited by 79 · see citing works
Mortality study of 18 000 patients treated with omeprazole
Bateman, D. N., Colin-Jones, D. G., Hartz, S. C., Langman, M. J. S., Logan, R. F., Mant, J., Murphy, M., Paterson, K. R., Rowsell, R., Thomas, S., et al. (2003) · Gut · doi:10.1136/gut.52.7.942 · Cited by 78 · see citing works
Nitrosamines : toxicology and microbiology
Hill, M. J. (1988) · Ellis Horwood eBooks · Cited by 75 · see citing works
Proton pump inhibitors and an emerging epidemic of gastric fundic gland polyposis
Freeman, H. J. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.1318 · Cited by 69 · see citing works
Gastric Polyps and Nodules in Children Receiving Long-Term Omeprazole Therapy
Pashankar, D. S., & Israel, D. M. (2002) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/00005176-200211000-00013 · Cited by 62 · see citing works
Cancer occurrence in a cohort of patients treated with cimetidine.
Møller, H., Lindvig, K., Klefter, R., Mosbech, J., & Jensen, O. M. (1989) · Gut · doi:10.1136/gut.30.11.1558 · Cited by 61 · see citing works
Elevated Serum Gastrin Levels in Patients with Colorectal Neoplasia
Seitz, E., Giovannini, M. F., Gouvernet, J., & Gautheir, A. P. (1991) · Journal of Clinical Gastroenterology · doi:10.1097/00004836-199110000-00013 · Cited by 58 · see citing works
Association Between Use of Acid-Suppressive Drugs and Risk of Gastric Cancer
Tamim, H., Duranceau, A., Chen, L.-Q., & LeLorier, J. (2008) · Drug Safety · doi:10.2165/00002018-200831080-00004 · Cited by 54 · see citing works
A morphometric study of neovascularization in colorectal carcinoma
Pavlopoulos, P. M., Konstantinidou, A. E., Agapitos, E. B., Kavantzas, N., Nikolopoulou, P., & Davaris, P. (1998) · Cancer · doi:10.1002/(sici)1097-0142(19981115)83:10 · Cited by 54 · see citing works
Postmarketing surveillance of the safety of cimetidine: 10 year mortality report.
Colin-Jones, D. G., Langman, M. J. S., Lawson, D. H., Logan, R., Paterson, K. R., & Vessey, M. P. (1992) · Gut · doi:10.1136/gut.33.9.1280 · Cited by 54 · see citing works
Use of cimetidine and other peptic ulcer drugs in Denmark 1977-1990 with analysis of the risk of gastric cancer among cimetidine users.
Møller, H., Nissen, A., & Mosbech, J. (1992) · Gut · doi:10.1136/gut.33.9.1166 · Cited by 50 · see citing works
Antisecretory drugs and gastric cancer.
LANGMAN, M. J. S. (1985) · BMJ · doi:10.1136/bmj.290.6485.1850 · Cited by 49 · see citing works
Observation of gastric glandular cysts in the corpus mucosa of the stomach under omeprazole treatment.
Stolte, M., Bethke, B., Seifert, E., Armbrecht, U., Lütke, A., Goldbrunner, P., & Rabast, U. (1995) · PubMed · Cited by 47 · see citing works
Effects of 5 years of treatment with rabeprazole or omeprazole on the gastric mucosa
Rindi, G., Fiocca, R., Morocutti, A., Jacobs, A., Miller, N., & Þjóðleifsson, B. (2005) · European Journal of Gastroenterology & Hepatology · doi:10.1097/00042737-200505000-00013 · Cited by 47 · see citing works
Long‐term lansoprazole treatment for gastro‐oesophageal reflux disease: clinical efficacy and influence on gastric mucosa
Geboes, K., Dekker, W., Mulder, C. J. J., Nusteling, K., & (ON BEHALF OF THE DUTCH STUDY GROUP) (2001) · Alimentary Pharmacology & Therapeutics · doi:10.1046/j.1365-2036.2001.01105.x · Cited by 47 · see citing works
Trophic effects of pentagastrin on gastrointestinal tract in fed and fasted rats
Solomon, T. E. (1986) · Gastroenterology · doi:10.1016/0016-5085(86)90446-4 · Cited by 45 · see citing works
Long term omeprazole therapy for reflux esophagitis: Follow-up in serum gastrin levels, EC cell hyperplasia and neoplasia
Singh, P. K. (2000) · World Journal of Gastroenterology · doi:10.3748/wjg.v6.i6.789 · Cited by 43 · see citing works
Histamine-2-receptor antagonists and gastric cancer risk
Vecchia, C. L., Negri, E., D’Avanzo, B., Vecchia, C. L., & Franceschi, S. (1990) · The Lancet · doi:10.1016/0140-6736(90)91888-h · Cited by 43 · see citing works
GASTRIC CANCER IN PATIENTS WHO HAVE TAKEN CIMETIDINE
Ruddell, W. S. J., Reed, P. I., Cassell, P. G., Walters, C. L., Hill, M. J., Taylor, T. V., Lee, D., Howatson, A. G., Anderson, J., Macleod, I. B., et al. (1979) · The Lancet · doi:10.1016/s0140-6736(79)91910-x · Cited by 35 · see citing works
GASTRIC CANCER IN PATIENTS WHO HAVE TAKEN CIMETIDINE
Elder, J. B., Ganguli, P. C., & Gillespie, I. E. (1979) · The Lancet · doi:10.1016/s0140-6736(79)90251-4 · Cited by 34 · see citing works
Effects of 6–12 Months of Esomeprazole Treatment on The Gastric Mucosa
Genta, R. M., Rindi, G., Fiocca, R., Magner, D. J., D'Amico, D., & Levine, D. S. (2003) · The American Journal of Gastroenterology · doi:10.1016/s0002-9270(03)00268-5 · Cited by 32 · see citing works
GASTRIC CANCER AFTER CIMETIDINE IN PATIENT WITH TWO NEGATIVE PRE-TREATMENT BIOPSIES
Hawker, P. C., Muscroft, T. J., & Keighley, M. R. B. (1980) · The Lancet · doi:10.1016/s0140-6736(80)92855-x · Cited by 30 · see citing works
A review of epidemiological studies on cancer in relation to the use of anti-ulcer drugs
Vecchia, C. L., & Tavani, A. (2002) · European Journal of Cancer Prevention · doi:10.1097/00008469-200204000-00002 · Cited by 29 · see citing works
Quantitative assessment of gastric corpus atrophy in subjects using omeprazole: a randomized follow-up study
van Grieken, N. C. T., Meijer, G. A., Weiss, M. M., Bloemena, E., Lindeman, J., Baak, J. P. A., Meuwissen, S. G. M., & Kuipers, E. J. (2001) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2001.04242.x · Cited by 28 · see citing works
Smoking and colorectal adenomas
Almendingen, K., Hofstad, B., Trygg, K. U., Hoff, G. S., Hussain, A., & Vatn, M. H. (2000) · European Journal of Cancer Prevention · doi:10.1097/00008469-200006000-00007 · Cited by 26 · see citing works
Effects of 6–12 Months of Esomeprazole Treatment on The Gastric Mucosa
Genta, R. M., Rindi, G., Fiocca, R., et al. (2003) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2003.07489.x · Cited by 24 · see citing works
Spontaneous resolution of multiple fundic gland polyps after cessation of treatment with lansoprazole and Nissen fundoplication: A case report
Kazantsev, G. B., Schwesinger, W. H., & Heim-Hall, J. M. (2002) · Gastrointestinal Endoscopy · doi:10.1067/mge.2002.122583 · Cited by 23 · see citing works
[Spontaneous resolution of multiple fundic gland polyps after cessation of treatment with omeprazole].
Kim, J. S., Chae, H. S., Kim, H.-K., Cho, Y., Park, Y.-W., Son, H.-S., Han, S.-W., & Choi, K.-Y. (2008) · PubMed · Cited by 21 · see citing works
Antacid Drug Use and Risk of Esophageal and Gastric Adenocarcinomas in Los Angeles County
Duan, L., Wu, A. H., Sullivan‐Halley, J., & Bernstein, L. (2009) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-08-0764 · Cited by 20 · see citing works
Histamine-2 Receptor Antagonists and Gastric Cancer
Johnson, A. G., Jick, S. S., Perera, D. R., & Jick, H. (1996) · Epidemiology · doi:10.1097/00001648-199607000-00016 · Cited by 20 · see citing works
Cimetidine Use and Gastric Cancer
Schumacher, M. C., Jick, S. S., Jick, H., & Feld, A. D. (1990) · Epidemiology · doi:10.1097/00001648-199005000-00012 · Cited by 19 · see citing works
Fundic gland polyps: three other case reports suggesting a possible association with acid suppressing therapy.
Vlierberghe, H. V., Vos, M. D., Cock, G. D., Cuvelier, C. A., & Elewaut, A. (1997) · PubMed · Cited by 16 · see citing works
A study to determine the sensitivity and specificity of hospital discharge diagnosis data used in the MICA study
McAlpine, R., Pringle, S. D., Pringle, T. H., Lorimer, R., & MacDonald, T. M. (1998) · Pharmacoepidemiology and Drug Safety · doi:10.1002/(sici)1099-1557(199809/10)7:5 · Cited by 11 · see citing works
Histamine-2-receptor antagonists and gastric cancer: update and note on latency and covariates.
Vecchia, C. L., Negri, E., Franceschi, S., & D’Avanzo, B. (1992) · PubMed · Cited by 8 · see citing works
Toxicology of N-nitroso compounds
Coulston, F., & Olajos, E. J. (1982) · Ecotoxicology and Environmental Safety · doi:10.1016/0147-6513(82)90083-5 · Cited by 6 · see citing works
GASTRIC CANCER AFTER CIMETIDINE IN PATIENT WITH TWO NEGATIVE PRE-TREATMENT BIOPSIES
Hawker, P. (1980) · The Lancet · doi:10.1016/s0140-6736(80)91197-6 · Cited by 5 · see citing works
Long term proton pump inhibitor (PPI) use and incidence of gastric (pre) malignant lesions.
Eslami, L., Kalantarian, S., Nasseri‐Moghaddam, S., & Majdzadeh, R. (2008) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007098 · Cited by 2 · see citing works
[A case of gastric fundic polyps during long-term treatment of reflux esophagitis with omeprazole].
Yamamoto, T., Matsumoto, J., Kosaihira, T., Nomoto, M., Kitajima, S., & Arima, T. (2003) · PubMed · Cited by 1 · see citing works

Flagged first, then by citations

Sorted by citations

ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease
Katz, P. O., Dunbar, K. B., Schnoll‐Sussman, F. H., Greer, K. B., Yadlapati, R. H., & Spechler, S. J. (2021) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000001538 · Cited by 1,064 · see citing works
Effective and safe proton pump inhibitor therapy in acid-related diseases – A position paper addressing benefits and potential harms of acid suppression
for the SIF-AIGO-FIMMG Group, Scarpignato, C., on behalf of the Italian Society of Pharmacology, T. I. A. O. H. G., Gatta, L., Zullo, A., & Blandizzi, C. (2016) · BMC Medicine · doi:10.1186/s12916-016-0718-z · Cited by 469 · see citing works
“pylori-infected patients [448], where the antisecretory effect is increased • No controlled human data support the increased risk of gastric cancer [92, 449] • More and higher quality studies are needed to confirm or refute any causal link with gastric cancer [450, 451] • No data support the increased risk of colorect…”
Result
The stomach in health and disease
Hunt, R. H., Camilleri, M., Crowe, S. E., El-Omar, E. M., Fox, J. G., Kuipers, E. J., Malfertheiner, P., McColl, K. E. L., Pritchard, D. M., Rugge, M., et al. (2015) · Gut · doi:10.1136/gutjnl-2014-307595 · Cited by 407 · see citing works
Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified
Bruno, G., Zaccari, P., Rocco, G., Scalese, G., Panetta, C., Porowska, B., Pontone, S., & Severi, C. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i22.2706 · Cited by 258 · see citing works
Proton pump inhibitors: Risks of long‐term use
Eusebi, L. H., Rabitti, S., Artesiani, M. L., Gelli, D., Montagnani, M., Zagari, R. M., & Bazzoli, F. (2017) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.13737 · Cited by 218 · see citing works
Management of epithelial precancerous conditions and early neoplasia of the stomach (MAPS III): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG) and European Society of Pathology (ESP) Guideline update 2025
Dinis-Ribeiro, M. J., Libânio, D., Uchima, H., Spaander, M. C. W., Bornschein, J., Matysiak‐Budnik, T., Tziatzios, G., Santos‐Antunes, J., Areia, M., Chapelle, N., et al. (2025) · Endoscopy · doi:10.1055/a-2529-5025 · Cited by 234 · see citing works
Use of Proton Pump Inhibitors and Risks of Fundic Gland Polyps and Gastric Cancer: Systematic Review and Meta-analysis
Tran‐Duy, A., Spaetgens, B., Hoes, A. W., de Wit, N. J., & Stehouwer, C. D. A. (2016) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2016.05.018 · Cited by 208 · see citing works
“4 (3-98) months in the study by Choudhry et al.”
Background
Maintenance therapy with proton pump inhibitors and risk of gastric cancer: a nationwide population-based cohort study in Sweden
Brusselaers, N., Wahlin, K., Engstrand, L., & Lagergren, J. (2017) · BMJ Open · doi:10.1136/bmjopen-2017-017739 · Cited by 204 · see citing works
“Decreased gastric acidity may also result in increased bacterial colonisation, including non-gastric micro-organisms, and a greater number of bacteria that produce nitrosamines, which are well-established carcinogens of the gastric mucosa.(5) 33 The impact of these proposed underlying mechanisms may also be person-dep…”
BackgroundInfluential
The role of the gastrointestinal microbiome in Helicobacter pylori pathogenesis
Sheh, A., & Fox, J. G. (2013) · Gut Microbes · doi:10.4161/gmic.26205 · Cited by 199 · see citing works
Proton pump inhibitor therapy and potential long-term harm
Corleto, V. D., Festa, S., Giulio, E. D., & Annibale, B. (2013) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000031 · Cited by 134 · see citing works
Histamine receptors and cancer pharmacology: an update
Massari, N. A., Nicoud, M. B., & Medina, V. A. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14535 · Cited by 131 · see citing works
“However, acid suppressive drugs such as H2 receptor antagonists are also associated with an increased risk of GC (Ahn et al., 2013).”
Background
Vonoprazan prevents low-dose aspirin-associated ulcer recurrence: randomised phase 3 study
Kawai, T., Oda, K., Funao, N., Nishimura, A., Matsumoto, Y., Mizokami, Y., Ashida, K., & Sugano, K. (2017) · Gut · doi:10.1136/gutjnl-2017-314852 · Cited by 124 · see citing works
Oesophageal adenocarcinoma and gastric cancer: should we mind the gap?
Hayakawa, Y., Sethi, N. S., Sepulveda, A. R., Bass, A. J., & Wang, T. C. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.24 · Cited by 118 · see citing works
Gastric Parietal Cell Physiology and Helicobacter pylori–Induced Disease
Yao, X., & Smolka, A. J. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.02.036 · Cited by 112 · see citing works
Identification of quinoline-chalcone hybrids as potential antiulcer agents
Sashidhara, K. V., Avula, S. R., Mishra, V. K., Palnati, G. R., Singh, L., Singh, N., Chhonker, Y. S., Swami, P., Bhatta, R. S., & Palit, G. (2014) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2014.10.068 · Cited by 103 · see citing works
Meta-analyses including non-randomized studies of therapeutic interventions: a methodological review
Faber, T., Ravaud, P., Riveros, C., Perrodeau, É., & Dechartres, A. (2016) · BMC Medical Research Methodology · doi:10.1186/s12874-016-0136-0 · Cited by 101 · see citing works
Changes in proton pump inhibitor prescribing trend over the past decade and pharmacists’ effect on prescribing practice at a tertiary hospital
Luo, H., Fan, Q., Xiao, S., & Chen, K. (2018) · BMC Health Services Research · doi:10.1186/s12913-018-3358-5 · Cited by 100 · see citing works
Local Acetaldehyde—An Essential Role in Alcohol-Related Upper Gastrointestinal Tract Carcinogenesis
Nieminen, M. T., & Salaspuro, M. P. (2018) · Cancers · doi:10.3390/cancers10010011 · Cited by 95 · see citing works
“â Long-term use of drugs suppressing gastric acid secretion (PPIs, H2-blockers) [111]: Microbial colonization of stomach results in enhanced local ACH production from ethanol [32,119]”
Background
Mitogen-Activated Protein Kinase Signal Transduction in Solid Tumors
Lei, Y., Wang, W., Mei, J.-H., & Wang, C. (2014) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2014.15.20.8539 · Cited by 92 · see citing works
“, 2014), and acid suppressive drugs such as H2R blocker or PPI may act as a stimulator for gastric cancer (Ahn et al., 2013).”
Background
Proton Pump Inhibitor Use and Risk of Gastric, Colorectal, Liver, and Pancreatic Cancers in a Community-Based Population
Lee, J. K., Merchant, S. A., Schneider, J. L., Jensen, C. D., FIREMAN, B. H., Quesenberry, C. P., & Corley, D. A. (2020) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000000591 · Cited by 91 · see citing works
The Safety of Appropriate Use of Over-the-Counter Proton Pump Inhibitors: An Evidence-Based Review and Delphi Consensus
Johnson, D. A., Katz, P. O., Armstrong, D., Cohen, H., Delaney, B. C., Howden, C. W., Katelaris, P., Tutuian, R. I., & Castell, D. O. (2017) · Drugs · doi:10.1007/s40265-017-0712-6 · Cited by 87 · see citing works
“The identified studies did not focus specifically on early gastric cancer; furthermore, they were biased by the populations that were assessed, as well as types of analyses [12, 17, 18, 33, 34].”
Background
Gastrin and Gastric Cancer
Smith, J. P., Nadella, S., & Osborne, N. (2017) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2017.03.004 · Cited by 81 · see citing works
Maintenance proton pump inhibition therapy and risk of oesophageal cancer
Brusselaers, N., Engstrand, L., & Lagergren, J. (2018) · Cancer Epidemiology · doi:10.1016/j.canep.2018.02.004 · Cited by 80 · see citing works
The Clinician’s Guide to Proton Pump Inhibitor Related Adverse Events
Elias, E. D., & Targownik, L. E. (2019) · Drugs · doi:10.1007/s40265-019-01110-3 · Cited by 68 · see citing works
Proton pump inhibitor: The dual role in gastric cancer
Joo, M. K., Park, J., & Chun, H. J. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i17.2058 · Cited by 65 · see citing works
Effects of ALDH2 Genotype, PPI Treatment and L-Cysteine on Carcinogenic Acetaldehyde in Gastric Juice and Saliva after Intragastric Alcohol Administration
Maejima, R., Iijima, K., Kaihovaara, P., Hatta, W., Koike, T., Imatani, A., Shimosegawa, T., & Salaspuro, M. P. (2015) · PLoS ONE · doi:10.1371/journal.pone.0120397 · Cited by 63 · see citing works
“A recent meta-analysis suggested that the use of acid-suppressive drugs is also associated with an increased risk of stomach cancer [32].”
Background
The Esophageal and Gastric Microbiome in Health and Disease
Hunt, R. H., & Yaghoobi, M. (2017) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2016.09.009 · Cited by 63 · see citing works
Randomised trial of acid inhibition by vonoprazan 10/20 mg once daily vs rabeprazole 10/20 mg twice daily in healthy Japanese volunteers (SAMURAI pH study)
Takeuchi, T., Furuta, T., Fujiwara, Y., Sugimoto, M., Kasugai, K., Kusano, M., Okada, H., Suzuki, T., Higuchi, T., Kagami, T., et al. (2020) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.15641 · Cited by 62 · see citing works
Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis
Segna, D., Brusselaers, N., Glaus, D., Krupka, N., & Misselwitz, B. (2021) · Therapeutic Advances in Gastroenterology · doi:10.1177/17562848211051463 · Cited by 56 · see citing works
Proton pump inhibitors on pancreatic cancer risk and survival
Kearns, M. D., Boursi, B., & Yang, Y. (2017) · Cancer Epidemiology · doi:10.1016/j.canep.2016.12.006 · Cited by 56 · see citing works
“In spite of a highly suggestive mechanism demonstrated in experimental models linking PPI use, and increased gastrin levels to GI cancers, the results of epidemiologic studies have been mixed; several studies showed increased rates of gastric cancer among PPI users (24– 26) while other studies found no link between ac…”
Result
Helicobacter pylori Infection Synergistic with IL-1β Gene Polymorphisms Potentially Contributes to the Carcinogenesis of Gastric Cancer
Hong, J., Zuo, W., Wang, A., & Lü, N. (2016) · International Journal of Medical Sciences · doi:10.7150/ijms.14239 · Cited by 51 · see citing works
“increased risk of GC through inhibition of gastric acid secretion [54].”
Background
Relationship between long‐term use of proton pump inhibitors and risk of gastric cancer: A systematic analysis
Jiang, K., Jiang, X., Wen, Y., Liao, L., & Liu, F. (2019) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.14759 · Cited by 46 · see citing works
Prevention of gastric cancer by Helicobacter pylori eradication: A review from Japan
Uno, Y. (2019) · Cancer Medicine · doi:10.1002/cam4.2277 · Cited by 45 · see citing works
Impact of clinical pharmacist interventions on inappropriate prophylactic acid suppressant use in hepatobiliary surgical patients undergoing elective operations
Luo, H., Fan, Q., Xiao, S., & Chen, K. (2017) · PLoS ONE · doi:10.1371/journal.pone.0186302 · Cited by 41 · see citing works
Use of proton pump inhibitors and histamine-2 receptor antagonists and risk of gastric cancer in two population-based studies
Liu, P., McMenamin, Ú. C., Johnston, B. T., Murchie, P., Iversen, L., Lee, A. J., Vissers, P. A. J., & Cardwell, C. R. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-0860-4 · Cited by 37 · see citing works
Proton pump inhibitors and dementia risk: Evidence from a cohort study using linked routinely collected national health data in Wales, UK
Cooksey, R., Kennedy, J. I., Dennis, M., Escott‐Price, V., Lyons, R. A., Seaborne, M., & Brophy, S. T. (2020) · PLoS ONE · doi:10.1371/journal.pone.0237676 · Cited by 37 · see citing works
“Some of the safety concerns associated with long-term use of PPIs include: cancer (11,12) masking 59 symptoms of other underlying conditions (13), infections (14–18), celiac disease (19), vitamin-B12 60 deficiency (20), abnormal kidney function (21,22), and more recently, dementia (23,24).”
Background
Safety of proton pump inhibitors and risk of gastric cancers: review of literature and pathophysiological mechanisms
Ko, Y., Tang, J., Sanagapalli, S., Kim, B. S. M., & Leong, R. W. L. (2015) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2016.1118050 · Cited by 35 · see citing works
Key role of local acetaldehyde in upper GI tract carcinogenesis
Salaspuro, M. P. (2017) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2017.09.016 · Cited by 34 · see citing works
Risk of gastric cancer, gastrointestinal cancers and other cancers: a comparison of treatment with pantoprazole and other proton pump inhibitors
Schneider, J. L., Kolitsopoulos, F. M., & Corley, D. A. (2015) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13450 · Cited by 34 · see citing works
Effectiveness and Safety of Histamine H2 Receptor Antagonists: An Umbrella Review of Meta‐Analyses
Meng, R., Chen, L., Zhang, M., Cai, W., Yin, S., Fan, Y., Zhou, T. Y., Huang, Y., & He, G. (2022) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.2147 · Cited by 30 · see citing works
Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer
Paz, M. F. C. J., de Alencar, M. V. O. B., de Lima, R. M. P., Sobral, A. L. P., do Nascimento, G. T. M., dos Reis, C. A., Coêlho, M. D. P. S. D. S., do Nascimento, M. L. L. B., Júnior, A. L. G., Machado, K. D. C., et al. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/3457890 · Cited by 30 · see citing works
“5-40mg/kg Clinical Human (n = 94558) H2 receptor antagonists and PPIs Oxidative stress [57]”
Background
The role of gastric microecological dysbiosis in gastric carcinogenesis
Huang, H., Zhong, W., Wang, X., Yang, Y. Z., Wu, T., Chen, R., Liu, Y., He, F., & Li, . (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1218395 · Cited by 31 · see citing works
“This shift can trigger hypochlorhydria, a condition that reduces microbial diversity, fosters proliferation of genotoxic microorganisms, and heightens activity of bacterial nitrate/ nitrite reductases, ultimately leading to conversion of nitrite and other nitrogenous compounds in gastric fluid to cancer-associated N-n…”
Background
Synthesis and in vivo anti-ulcer evaluation of some novel piperidine linked dihydropyrimidinone derivatives
Bhat, M. A., Al-Omar, M. A., & Naglah, A. M. (2018) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2018.1474212 · Cited by 27 · see citing works
“4-(3-Nitrophenyl)-5-[4-(piperidin-1-yl) benzoyl]-3,4-dihydropyrimidin-2(1H)-one (4): colour: yellow; yield: m.”
Gastrointestinal Hormones ☆
Gribble, F. M., Reimann, F. M., & Roberts, G. P. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-809954-4.00002-5 · Cited by 27 · see citing works
The Safety of Long-term Daily Usage of a Proton Pump Inhibitor: A Literature Review
Abbas, M. K., Zaidi, A. R. Z., Robert, C. A., Thiha, S., & Malik, B. H. (2019) · Cureus · doi:10.7759/cureus.5563 · Cited by 26 · see citing works
Gut Bless Your Pain—Roles of the Gut Microbiota, Sleep, and Melatonin in Chronic Orofacial Pain and Depression
Lassmann, Ł., Pollis, M., Żółtowska, A., & Manfredini, D. (2022) · Biomedicines · doi:10.3390/biomedicines10071528 · Cited by 25 · see citing works
Proton Pump Inhibitors and Cancer Risk
Zhang, M., Fan, Y., Meng, R., Cai, W., Yin, S., Zhou, T. Y., Huang, Y., Wang, P., Jiang, F., Yang, M. X., et al. (2022) · American Journal of Clinical Oncology · doi:10.1097/coc.0000000000000949 · Cited by 26 · see citing works
Negative Association of Proton Pump Inhibitors With Subsequent Development of Breast Cancer: A Nationwide Population‐Based Study
Chen, C., Lee, C., Lin, Y., Kao, L., & Lin, H. (2018) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.1329 · Cited by 24 · see citing works
Effect of frequently prescribed drugs on gastric cancer risk
Weltermann, T., Schulz, C., & Macke, L. (2021) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2021.101741 · Cited by 24 · see citing works
Comprehensive analysis of proton pump inhibitors and risk of digestive tract cancers
Zeng, R., Cheng, Y., Luo, D., Wang, J., Yang, J. H., Jiang, L., Zhuo, Z., Guo, K., Wu, H., Leung, F. W., et al. (2021) · European Journal of Cancer · doi:10.1016/j.ejca.2021.07.030 · Cited by 24 · see citing works
Does the Use of Proton Pump Inhibitors Increase the Risk of Pancreatic Cancer? A Systematic Review and Meta-Analysis of Epidemiologic Studies
Hong, H.-E., Kim, A., Kim, M.-R., Ko, H., & Jung, M. K. (2020) · Cancers · doi:10.3390/cancers12082220 · Cited by 24 · see citing works
Gastric Microbiota: Tracing the Culprit
Petra, C. V., Rus, A., & Dumitrascu, D. L. (2017) · Medicine and Pharmacy Reports · doi:10.15386/cjmed-854 · Cited by 23 · see citing works
“Interestingly, Ahn and colleagues conducted a meta-analysis which reported that acid suppressive drugs are associated with an increased risk of gastric cancer [12].”
Background
Exposure to proton pump inhibitors and risk of pancreatic cancer: a meta-analysis
Alkhushaym, N., Almutairi, A. R., Althagafi, A. A., Fallatah, S., Oh, M., Martin, J. R., Babiker, H. M., McBride, A., & Abraham, I. L. (2020) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2020.1715939 · Cited by 22 · see citing works
Rebuilding trust in proton pump inhibitor therapy
Turshudzhyan, A., Samuel, S. B., Tawfik, A., & Tadros, M. S. (2022) · World Journal of Gastroenterology · doi:10.3748/wjg.v28.i24.2667 · Cited by 22 · see citing works
Inhibiting the proton pump: mechanisms, benefits, harms, and questions
Aronson, J. K. (2016) · BMC Medicine · doi:10.1186/s12916-016-0724-1 · Cited by 22 · see citing works
“Recent systematic reviews also suggest an association [25, 26], and this problem needs further study.”
Background
Silencing of ATP4B of ATPase H+/K+ Transporting Beta Subunit by Intragenic Epigenetic Alteration in Human Gastric Cancer Cells
Lin, S., Lin, B., Wang, X., Pan, Y., Xu, Q., He, J., Gong, W., Xing, R., He, Y., Guo, L., et al. (2017) · Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics · doi:10.3727/096504016x14734735156265 · Cited by 22 · see citing works
Bioelectric pharmacology of cancer: A systematic review of ion channel drugs affecting the cancer phenotype
Kofman, K., & Levin, M. G. (2024) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2024.07.005 · Cited by 20 · see citing works
Proton Pump Inhibitors and Cognitive Health: Review on Unraveling the Dementia Connection and Co-morbid Risks
Khan, Z., Mehan, S., Saifi, M. A., Gupta, G. D., Narula, A. S., & Kalfin, R. E. (2023) · Current Alzheimer Research · doi:10.2174/0115672050289946240223050737 · Cited by 20 · see citing works
The association between acid-suppressive agent use and the risk of cancer: a systematic review and meta-analysis
Song, H. J., Jeon, N., & Squires, P. J. (2020) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-020-02927-8 · Cited by 19 · see citing works
Continuous improvement on the rationality of prophylactic injectable PPIs usage by a clinical pharmacist-led guidance team at a Chinese tertiary teaching hospital
Hong, Y. K., Ye, Z., Gao, Z., & Rao, Y. (2020) · Journal of International Medical Research · doi:10.1177/0300060520954729 · Cited by 18 · see citing works
“Furthermore, it has been reported that PIPU is not cost-effective, except in high-risk patients.(34) A survey revealed that some clinicians feel that PPIs are harmless and can be used by anyone.”
Background
Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review)
Fisher, L., Fisher, A., & Smith, P. N. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9103253 · Cited by 18 · see citing works
Risk factors for gastric cancer: an umbrella review of systematic reviews and meta-analyses
Liang, J., Yuan, H., Quan, C., & Chen, J. Q. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1564575 · Cited by 18 · see citing works
Acid-suppressing therapies and subsite-specific risk of stomach cancer
Wennerström, C., Simonsen, J., Camargo, M. C., & Rabkin, C. S. (2017) · British Journal of Cancer · doi:10.1038/bjc.2017.84 · Cited by 17 · see citing works
“…including one in a county of Denmark (Poulsen et al, 2009), have reported significant associations of acid-suppressive drugs with increased risks of stomach cancer overall, even after exclusion of cancers within the first few years of exposure to address confounding by indication (Ahn et al, 2013).”
Background
Proton pump inhibitors and the risk of gastric cancer: a systematic review, evidence synthesis and life course epidemiology perspective
Brusselaers, N., Kamal, H., Graham, D. Y., & Engstrand, L. G. (2025) · BMJ Open Gastroenterology · doi:10.1136/bmjgast-2024-001719 · Cited by 15 · see citing works
Comparison of Estimates between Cohort and Case–Control Studies in Meta-Analyses of Therapeutic Interventions: A Meta-Epidemiological Study
Lanza, A. L., Ravaud, P., Riveros, C., & Dechartres, A. (2016) · PLoS ONE · doi:10.1371/journal.pone.0154877 · Cited by 15 · see citing works
Association between proton pump inhibitors after percutaneous coronary intervention and risk of gastric cancer
Ng, A. K., Ng, P. Y., Ip, A., Cheung, K. S., & Siu, C. (2021) · BMJ Open Gastroenterology · doi:10.1136/bmjgast-2021-000719 · Cited by 15 · see citing works
Risk factors for gastric cancer: is it time to discard PPIs?
Laterza, L., Scaldaferri, F., & Gasbarrini, A. (2018) · Gut · doi:10.1136/gutjnl-2017-315621 · Cited by 15 · see citing works
Long-term proton pump inhibitor use and the incidence of gastric cancer: A systematic review and meta-analysis
Lin, J., Lin, J.-X., Zheng, C., Xie, J., Wang, J.-B., Lu, J., Chen, Q., Cao, L., Lin, M., Li, P., et al. (2020) · Journal of Gastric Surgery · doi:10.36159/jgs.v2i1.17 · Cited by 13 · see citing works
Use of histamine‐2 receptor antagonists and risk of inflammatory bowel diseases: A systematic review and meta‐analysis of observational studies
Dsa, F. F., Fernandes, E. Z., Kesarkar, S. V., Swaminathan, L., Kunhikatta, V., Rashid, M., Thunga, G., Chandran, V. P., & Nair, S. (2022) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/jcpt.13662 · Cited by 13 · see citing works
Can a gastric cancer risk survey identify high-risk patients for endoscopic screening? A pilot study
In, H., Langdon-Embry, M., Gordon, L., Schechter, C. B., Wylie‐Rosett, J., Castle, P. E., Kemeny, M. M., & Rapkin, B. D. (2018) · Journal of Surgical Research · doi:10.1016/j.jss.2018.02.053 · Cited by 11 · see citing works
Changing trends in cancer incidence of upper aerodigestive tract and stomach in Japanese alcohol‐dependent men (1993‐2018)
Yokoyama, A., Omori, T., & Yokoyama, A. (2019) · Cancer Medicine · doi:10.1002/cam4.2737 · Cited by 10 · see citing works
Ranitidine Use and Gastric Cancer Among Persons with Helicobacter pylori
Kumar, S., Goldberg, D. S., & Kaplan, D. E. (2021) · Digestive Diseases and Sciences · doi:10.1007/s10620-021-06972-w · Cited by 9 · see citing works
RNA Sequencing of Early-Stage Gastric Adenocarcinoma Reveals Multiple Activated Pathways and Novel Long Non-Coding RNAs in Patient Tissue Samples
Fattahi, S., Nikbakhsh, N., Taheri, H., Ranaee, M., & Akhavan‐Niaki, H. (2021) · Reports of Biochemistry and Molecular Biology · doi:10.52547/rbmb.9.4.478 · Cited by 9 · see citing works
“A meta-analysis of observational studies on the effect of acid suppressive drugs on the development of GC found that H2 receptor blockers, H2 receptor antagonists (H2Ras), and PPIs significantly increased the risk for GC (26).”
Background
Gastric cancer in the pediatric population, a multicenter cross-sectional analysis of presentation and coexisting comorbidities
Attard, T. M., Uraizee, O., Glynn, E. F., Stoecklein, N., Peter, S. D. S., & Thomson, M. A. (2022) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-022-03972-9 · Cited by 8 · see citing works
“Long-term antacid therapy, both proton pump inhibitor (PPI) as well as histamine-2 receptor antagonists (H2RAs), are associated with gastric neoplasia (Ahn et al. 2013).”
Background
Long-term safety and effectiveness of vonoprazan for prevention of gastric and duodenal ulcer recurrence in patients on nonsteroidal anti-inflammatory drugs in Japan: a 12-month post-marketing surveillance study
Kawai, T., Suzuki, C., Honda, Y., & Fernandez, J. L. (2022) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2023.2136163 · Cited by 8 · see citing works
Exposure to Commonly Used Drugs and the Risk of Gastric Cancer: An Umbrella Review of Meta-Analyses
Bai, X., Ding, S., Zhang, X., Han, M.-H., & Dai, D. (2023) · Cancers · doi:10.3390/cancers15020372 · Cited by 8 · see citing works
“never users 7 2253/1,136,484 Ahn [41], 2013 South Korea Acid suppressive drugs GC Any users vs.”
BackgroundInfluential
Prenatal and Early Childhood Exposure to Proton Pump Inhibitors and Antibiotics and the Risk of Childhood Cancer: A Nationwide Population-Based Cohort Study
Guðnadóttir, U., Fransson, E., Ljungman, G., Wikman, A., Vlieghe, E., Engstrand, L. G., & Brusselaers, N. (2024) · Drug Safety · doi:10.1007/s40264-024-01500-x · Cited by 7 · see citing works
Use of Proton Pump Inhibitors and the Risk for the Development of Gastric Cancers: A Nationwide Population-Based Cohort Study Using Balanced Operational Definitions
Gong, E. J., Bang, C. S., Kim, D., Lee, J. J., & Baik, G. H. (2022) · Cancers · doi:10.3390/cancers14205172 · Cited by 7 · see citing works
Intake of Proton-Pump Inhibitors and Gastric Cancer within the Stomach Cancer Pooling (StoP) Project
Sassano, M., Mariani, M., Pelucchi, C., Lunet, N., Morais, S., Martín, V., Moreno, V. R., Curado, M. P., Dias‐Neto, E., Leja, M., et al. (2023) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-23-0241 · Cited by 7 · see citing works
Proton Pump Inhibitors: Are They a Real Threat to the Patient?
Xavier, S. A., Magalhães, J. T., & Cotter, J. B. (2018) · GE Portuguese Journal of Gastroenterology · doi:10.1159/000487154 · Cited by 7 · see citing works
The role of 5α‐reductase inhibitors in gastro‐oesophageal cancer risk: A nested case‐control study
Busby, J., Karasneh, R. A., Murchie, P., McMenamin, Ú. C., Gadalla, S. M., Camargo, M. C., Iversen, L., Lee, A. J., Spence, A. D., & Cardwell, C. R. (2019) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.4909 · Cited by 7 · see citing works
Histamine N-methyltransferase upregulation, cardiac hypertrophy, and heart failure
Zhang, J., Jiang, H., Liu, L., Li, X., Hong, W., Xu, L., Dong, Z., Xu, Z., Gao, J., Sun, X., et al. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf1065 · Cited by 6 · see citing works
“12 These limitations underscore the need to explore safer and more effective therapeutic targets within the histamine pathway.”
Neoplasm Reports in Food and Drug Administration Adverse Event Reporting System Following Angiotensin Receptor Blocker Recalls
Sedgh, R. C., Moon, J., & Jackevicius, C. A. (2021) · Circulation Cardiovascular Quality and Outcomes · doi:10.1161/circoutcomes.120.007476 · Cited by 5 · see citing works
PPIs and gastric cancer: any causal relationship?
Crafa, P., Franceschi, M., Rodriguez-Castro, K. I., Franzoni, L., Russo, M., Brandimarte, G., Tursi, A., Rugge, M., & Mario, F. D. (2023) · Acta bio-medica dell'Ateneo parmense/Acta biomedica · doi:10.23750/abm.v94i3.14105 · Cited by 5 · see citing works
Pharmacokinetic evaluation of esomeprazole for the treatment of gastroesophageal reflux disease
Goirand, F., Ray, I. L., & Bardou, M. (2014) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2014.939627 · Cited by 4 · see citing works
“64]), but the results must be interpreted with caution as there was no information about Helicobacter pylori status of patients [111].”
Result
In Vitro and In Vivo Study of Argyreia speciosa on Chronic Gastric Ulceration and Metabolic Studies
Azmi, L., Shukla, I., Gupta, S. S., Yadav, N. P., Kant, P., & Rao, C. V. (2018) · Proceedings of the National Academy of Sciences India Section B Biological Sciences · doi:10.1007/s40011-018-1023-8 · Cited by 4 · see citing works
A Comprehensive Review on Omeprazole: Pharmacological Effects and Its Adverse Effects
Kumar, A., Sahani, V., & Patil, S. (2025) · Journal for Research in Applied Sciences and Biotechnology · doi:10.55544/jrasb.4.1.4 · Cited by 3 · see citing works
Omeprazole and adenocarcinoma in the stomach of rats submitted to duodenogastric reflux. Is there a protective effect?
Monteiro, R. L. R., Rodrigues, M. A. M., Araújo, M. R., Monteiro, D. R., & Andreollo, N. A. (2020) · Acta Cirúrgica Brasileira · doi:10.1590/s0102-865020200090000004 · Cited by 3 · see citing works
Efficacy of Vonoprazan in Nonsteroidal Anti‐Inflammatory Drug‐Induced Ulcer in Terms of Ulcer Recurrence and Gastrointestinal Bleeding: A Systematic Review and Meta‐Analysis
Bandyopadhyay, S. K., Samajdar, S. S., & Das, S. (2025) · Gastroenterology Research and Practice · doi:10.1155/grp/5625149 · Cited by 2 · see citing works
Inibidores da bomba de prótons e carcinogênese: uma revisão da literatura
Melo, I. D. O., de Carvalho, T. H. F., Cassundé, M. A., & Costa, R. B. (2021) · Revista de Medicina · doi:10.11606/issn.1679-9836.v100i5p479-485 · Cited by 2 · see citing works
Presence of Fundic Gland Polyps in Patients Undergoing Upper Gastrointestinal Endoscopy: Incidence and the Relation with the Use of Proton Pump Inhibitors
Loffeld, R. (2017) · Journal of Clinical Gastroenterology and Treatment · doi:10.23937/2469-584x/1510048 · Cited by 1 · see citing works
Association between proton pump inhibitor use and the risk of hepatobiliary cancers: A meta‐analysis
Yi, T.-Y., Peng, T., Wu, T., & Wu, A. (2024) · Advances in digestive medicine · doi:10.1002/aid2.13386 · Cited by 1 · see citing works
Acid Secretory Inhibitors and the Risk of Development of Gastric Cancer
Bang, C. S., & Baik, G. H. (2019) · The Korean Journal of Helicobacter and Upper Gastrointestinal Research · doi:10.7704/kjhugr.2019.19.1.73 · Cited by 1 · see citing works
Acid Suppressive Drugs
Shin, C. M. (2022) · The Korean Journal of Helicobacter and Upper Gastrointestinal Research · doi:10.7704/kjhugr.2022.0016 · Cited by 1 · see citing works
Gastrin and gastric cancer
&NA; (1993) · European Journal of Gastroenterology & Hepatology · doi:10.1097/00042737-199303000-00011 · Cited by 1 · see citing works
Effects of Acupuncture at SP6 on Reflux Esophagitis in Rats※
Lee, Y. K., Rho, S. S., & Kim, J. S. (2015) · 대한침구학회지 · doi:10.13045/acupunct.2015041
Prescription of Proton Pump Inhibitors in Elderly Subjects in Real Life: A Retrospective Study in a Gastroenterology Department
Boudabbous, M., Gdoura, H., Mnif, L., Chtourou, L., Grati, A., Amouri, A., & Tahri, N. (2017) · InTech eBooks · doi:10.5772/intechopen.70526
“Other potential unwanted effects of the PPI were described in the literature, in particularly the elderly, such as: • The consequences of the malabsorption: hyponatremia [17, 18], deficiency in vitamin B12 [19] and hypomagnesemia [20, 21] (which could have serious consequences such as confusion [22, 23]) • The infecti…”
Background
Long Term Use of Proton Pump Inhibitors: Where to Draw the Line
Haque, M. M. (2018) · Integrative Gastroenterology and Hepatology · doi:10.18314/igh.v1i1.1185
“Increased number of higher quality studies are needed to confirm or refute any causal link of PPIs with gastric cancer [113].”
Background
Doença do refluxo gastroesofágico no idoso
Nasi, A., & Queiroz, N. C. M. (2019) · doi:10.22288/978857868372600004
Proton Pump Inhibitor Controversies
Jaworek, A. J. (2020) · Springer eBooks · doi:10.1007/978-3-030-48890-1_31

Association Between Use of Acid-Suppressive Drugs and Risk of Gastric Cancer
Tamim, H., Duranceau, A., Chen, L.-Q., & LeLorier, J. (2008) · Drug Safety · doi:10.2165/00002018-200831080-00004 · Cited by 54 · see citing works
S1427 Is Acid Suppression Therapy Associated With Increased Risk of Cardia Gastric Cancer? A Meta-Analysis
Sun, C., Chen, Y., Ismail, M. R., Tuason, J. P. W., Cheng, X., Hu, L., Bhan, C., Kim, N. H., Prasad, A., Manem, N., et al. (2021) · The American Journal of Gastroenterology · doi:10.14309/01.ajg.0000779240.78130.d8 · Cited by 2 · see citing works
Meta‐analysis: Use of proton pump inhibitors and risk of gastric cancer in patients requiring gastric acid suppression
Piovani, D., Tsantes, A. G., Schünemann, H. J., & Bonovas, S. (2022) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.17360 · Cited by 28 · see citing works
Use of Proton Pump Inhibitors vs Histamine 2 Receptor Antagonists for the Risk of Gastric Cancer: Population-Based Cohort Study
Shin, G., Park, J. M., Hong, J., Cho, Y. K., Yim, H. W., & Choi, M. (2021) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000001167 · Cited by 37 · see citing works
Acid Suppression and Subsequent Gastric or Esophageal Cancer
Bjorkman, D. J., Msph, & Sm (2007) · Journal watch · doi:10.1056/jg200702230000002

Authors: Ahn, J. S.
Affiliations: Seoul National University (KR)
Corresponding author: Ahn, Jeong Soo
Venue: World Journal of Gastroenterology
Publisher: Baishideng Publishing Group Inc.
Published: 2013
Volume: 19
Issue: 16
Pages: 2560
ISSN: 1007-9327 (ISSN-L)
DOI: 10.3748/wjg.v19.i16.2560
PMC: PMC3646149
OpenAlex: W2056076454
Cited by: 109
References: 73
Citations by year: 2025: 6 · 2024: 6 · 2023: 5 · 2022: 13 · 2021: 9 · 2020: 14 · 2019: 11 · 2018: 13 · 2017: 14 · 2016: 7 · 2015: 5 · 2014: 3 · 2013: 2
FWCI: 1.00
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
Locations: World Journal of Gastroenterology (publishedVersion, cc-by-nc)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Research Foundation
National Research Foundation of Korea
National Cancer Institute (R25CA087949)
Topics: Health Sciences › Medicine › Surgery › Helicobacter pylori-related gastroenterology studies
Health Sciences › Medicine › Gastroenterology › Gastroesophageal reflux and treatments
Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
Keywords: acid-suppressive drugs, gastric cancer, H2 receptor antagonists, proton pump inhibitors, gastric cancer risk, drug-induced cancer risk
MeSH terms: Adolescent, Adult, Aged, Aged, 80 and over, Female, Histamine H2 Antagonists, Humans, Male, Middle Aged, Risk Factors, Stomach Neoplasms, Odds Ratio, Risk Assessment, Proton Pump Inhibitors, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Acid suppressive drugs and gastric cancer: A meta-analysis of observational studies

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks