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

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

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Ahn, Jeong Soo·2013·World Journal of Gastroenterology

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

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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.

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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
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
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
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
Untitled work
(2014) · Medical Entomology and Zoology · Cited by 17,633
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
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 2,724
Changing patterns in the incidence of esophageal and gastric carcinoma in the United States
Devesa, S. S., Blot, W. J., & Fraumeni, J. F. (1998) · Cancer · doi:10.1002/(sici)1097-0142(19981115)83:10 · Cited by 2,098
A human model of gastric carcinogenesis.
Corréa, P. (1988) · PubMed · Cited by 1,433
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

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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
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
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
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
“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
“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
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
“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
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
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
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
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
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
“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
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
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
“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
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
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
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
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
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
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
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
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
Gastrin and gastric cancer
&NA; (1993) · European Journal of Gastroenterology & Hepatology · doi:10.1097/00042737-199303000-00011 · Cited by 1
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

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 › Gastroenterology › Helicobacter pylori-related gastroenterology studies
Health Sciences › Medicine › Gastroenterology › Gastroesophageal reflux and treatments
Health Sciences › Medicine › Pharmacology (medical) › 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

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

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