Use of proton pump inhibitors and histamine-2 receptor antagonists and risk of gastric cancer in two population-based studies

Li, Peipei; McMenamin, Úna C.; Johnston, Brian T.; Murchie, Peter; Iversen, Lisa; Lee, Amanda; Vissers, Pauline A. J.; Cardwell, Chris R

doi:10.1038/s41416-020-0860-4

Cited by 21 publications

(61 citation statements)

References 38 publications

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“…Our secondary analysis using newly calculated unadjusted OR from raw binary outcome data from all 13 studies 15 – 17,27 – 31,33 – 35,37 yielded similar results (OR: 2.05, 95% CI: 1.54–2.64, I 2 = 91%, p < 0.01). Stratified analyses according to study design showed a higher GC risk estimate in the five included retrospective cohort studies 17,28 – 31 (OR: 2.76, 95% CI: 1.56–4.88, I 2 = 63%, p = 0.03) than in the eight included case-control studies 15 – 17,27,33–35,37 (OR: 1.59, 95% CI: 1.23–2.05, I 2 = 81%, p < 0.01, Supplemental Appendix Figure 3).…”

Section: Resultsmentioning

confidence: 64%

“…On a study level, Niikura et al 30 report a GC prevalence rate of 11% among PPI users, which is 22-fold higher than in another Asian collective from Hong Kong 31 (0.5%). Our secondary analysis using newly calculated unadjusted OR from raw binary outcome data from all 13 studies [15][16][17][27][28][29][30][31][33][34][35]37 yielded similar results (OR: 2.05, 95% CI: 1.54-2.64, I 2 = 91%, p < 0.01). Stratified analyses according to study design showed a higher GC risk estimate in the five included retrospective cohort studies 17,[28][29][30][31] (OR: 2.76, 95% CI: 1.56-4.88, I 2 = 63%, p = 0.03) than in the eight included casecontrol studies [15][16][17]27,[33][34][35]37 (OR: 1.59, 95% CI: 1.23-2.05, I 2 = 81%, p < 0.01, Supplemental Appendix Figure 3).…”

Section: Results From Quantitative Analysesmentioning

confidence: 89%

“…Association between GC and PPI use. Our metaanalysis of all 13 studies [15][16][17][27][28][29][30][31][33][34][35]37 indicated an increased GC risk in PPI users (OR: 1.94, 95% CI: 1.47-2.56, I 2 = 82%, p < 0.01) in random-effect models (Figure 1). The pooled GC prevalence of five retrospective cohort studies 17,28-31 was 0.6% (95% CI: 0.1-4%) among PPI users and 0.2% (95% CI: 0.04-1%) among non-users, both with high statistical heterogeneity (I 2 = 99%, p < 0.01, Supplemental Appendix Figure 4).…”

Section: Results From Quantitative Analysesmentioning

confidence: 99%

“…Seven out of 13 studies contributed to a stratified meta-analysis according to GC site. 17,27,29,[33][34][35]37 There was a significant risk increase in non-cardia GC (OR: 2.20, 95% CI: 1.44-3.36, I 2 = 77%) with a non-significant trend towards an increased risk in the cardia (OR: 1.77, 95% CI: 0.72-4.36, I 2 = 66%, Figure 2).…”

Section: Results From Quantitative Analysesmentioning

confidence: 99%

“…Moreover, we calculated the pooled prevalence of GC among PPI users and non-users in five retrospective cohort studies. 17,28–31…”

Section: Methodsmentioning

confidence: 99%

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Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis

Segna

Brusselaers

Glaus

et al. 2021

Therap Adv Gastroenterol

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Introduction: The use of proton-pump inhibitors (PPI) may be associated with an increased risk of gastric cancer (GC). Objective: To review and meta-analyse available literature investigating the association between PPI use and GC risk. Methods: Two independent reviewers systematically searched Ovid MEDLINE, EMBASE, and Cochrane Library (inception to July 2020) for case-control and cohort studies assessing the association between PPI use and GC according to a predefined protocol in PROSPERO (CRD42018102536). Reviewers independently assessed study quality, extracted data, and meta-analysed available and newly calculated odds ratios (ORs) using a random-effects model, and stratified for GC site (cardia versus non-cardia) and PPI duration (<1 year, 1–3 years, >3 years). Results: We screened 2,396 records and included five retrospective cohort and eight case-control studies comprising 1,662,881 individuals in our meta-analysis. In random-effect models, we found an increased GC risk in PPI users [OR: 1.94, 95% confidence interval (95% CI): 1.47–2.56] with high statistical heterogeneity ( I2 = 82%) and overall moderate risk of bias. Stratified analyses indicated a significant risk increase in non-cardia (OR: 2.20, 95% CI: 1.44–3.36, I2 = 77%) with a similar non-significant trend in cardia regions (OR: 1.77, 95% CI: 0.72–4.36, I2 = 66%). There was no GC increase with longer durations of PPI exposure (<1 year: OR: 2.29, 95% CI: 2.13–2.47, I2 = 0%; 1–3 years: OR: 1.46, 95% CI: 0.53–4.01, I2 = 35%; >3 years: OR: 2.08, 95% CI: 0.56–7.77, I2 = 61%). Conclusion: We found a twofold increased GC risk among PPI users, but this association does not confirm causation and studies are highly heterogeneous. PPI should only be prescribed when strictly indicated.

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Section: Resultsmentioning

confidence: 64%

Section: Results From Quantitative Analysesmentioning

confidence: 89%

Section: Results From Quantitative Analysesmentioning

confidence: 99%

Section: Results From Quantitative Analysesmentioning

confidence: 99%

“…Moreover, we calculated the pooled prevalence of GC among PPI users and non-users in five retrospective cohort studies. 17,28–31…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis

Segna

Brusselaers

Glaus

et al. 2021

Therap Adv Gastroenterol

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Gastroesophageal Reflux Disease

Maret-Ouda

Markar

Lagergren

2020

JAMA

187

179

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astroesophageal reflux disease (GERD) is defined by its cardinal symptoms (recurrent and troublesome heartburn and regurgitation) or by its specific complications (esophagitis, peptic strictures, and Barrett esophagus). 1 Barrett esophagus is a columnar metaplasia replacing parts of the native squamous cell epithelium that can progress to esophageal adenocarcinoma. 2 GERD can be a serious problem and should not be confused with less severe disease such as gastritis or the very common symptoms of dyspepsia or regurgitation that occur in almost all individuals without any underlying gastrointestinal pathology. GERD is caused by gastric contents' reaching the esophagus. Except for causing esophageal symptoms or complications, gastric juices can also reach more proximally (ie, into the pharynx, mouth, larynx, and airways) and cause or worsen various extraesophageal symptoms and conditions such as hoarseness, wheezing, cough, and asthma. 1 Established risk factors for developing GERD include increased body mass index, tobacco smoking, and genetic predisposition, 3 whereas infection with the gastric bacterium Helicobacter pylori can decrease this risk. 4 The prevalence of GERD is high and increasing, with greater rates in high-income countries (15%-25%) than in most low-and middle-income countries (<10%). 2,5 GERD can result in diminished health-related quality of life, and its prevalence and need for longterm treatment can consume substantial health care resources and result in high costs to society. 6,7 This review provides an update of the current evidence regarding GERD, with an emphasis on its clinical management in adults.IMPORTANCE Gastroesophageal reflux disease (GERD) is defined by recurrent and troublesome heartburn and regurgitation or GERD-specific complications and affects approximately 20% of the adult population in high-income countries.OBSERVATIONS GERD can influence patients' health-related quality of life and is associated with an increased risk of esophagitis, esophageal strictures, Barrett esophagus, and esophageal adenocarcinoma. Obesity, tobacco smoking, and genetic predisposition increase the risk of developing GERD. Typical GERD symptoms are often sufficient to determine the diagnosis, but less common symptoms and signs, such as dysphagia and chronic cough, may occur. Patients with typical GERD symptoms can be medicated empirically with a proton pump inhibitor (PPI). Among patients who do not respond to such treatment or if the diagnosis is unclear, endoscopy, esophageal manometry, and esophageal pH monitoring are recommended. Patients with GERD symptoms combined with warning symptoms of malignancy (eg, dysphagia, weight loss, bleeding) and those with other main risk factors for esophageal adenocarcinoma, such as older age, male sex, and obesity, should undergo endoscopy. Lifestyle changes, medication, and surgery are the main treatment options for GERD. Weight loss and smoking cessation are often useful. Medication with a PPI is the most common treatment, and after initial full-dose therapy, w...

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Core concepts in pharmacoepidemiology: Fundamentals of the cohort and case–control study designs

Pottegård

2022

Pharmacoepidemiology and Drug

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In this review paper, I outline the principles of the cohort as a sampling frame and provide a basic introduction to the cohort study design and the case-control study design, two of the most important designs in the pharmacoepidemiologist's toolbox.Further, I discuss when to prefer one design over the other. The paper is intended as a primer for people new to the field of pharmacoepidemiology and contains a range of suggestions for additional reading regarding the study designs and related epidemiological topics.

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Use of proton pump inhibitors and histamine-2 receptor antagonists and risk of gastric cancer in two population-based studies

Abstract: Use of proton pump inhibitors and histamine-2 receptor antagonists and risk of gastric cancer in two population-based studies.

Cited by 21 publications

References 38 publications

Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis

Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis

Gastroesophageal Reflux Disease

Core concepts in pharmacoepidemiology: Fundamentals of the cohort and case–control study designs

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