Chronic Proton Pump Inhibitor Therapy and the Risk of Colorectal Cancer
Open accessAbstract
Background & aims Chronic acid suppression by proton pump inhibitor therapy can lead to hypergastrinemia. Because existing evidence suggested an association between hypergastrinemia and colorectal cancer, we examined whether long-term proton pump inhibitor use is associated with an increased risk of colorectal cancer in a population-representative cohort.Methods We conducted a nested case-control study among patients 50 years of age and older and with > or =5 years of colorectal cancer-free initial follow-up in the General Practice Research Database (1987-2002) from the United Kingdom. Cases consisted of all patients with an incident diagnosis of colorectal cancer. Using incidence density sampling, up to 10 controls were matched with each case on practice site and both duration and calendar time of follow-up before the index date. The primary exposure of interest was > or =5 years of cumulative proton pump inhibitor therapy. We assessed the presence of duration-response and dose-response effects.Results We identified 4432 incident colorectal cancer cases and 44,292 controls. The adjusted odds ratio for > or =5 years of proton pump inhibitor exposure was 1.1 (95% confidence interval, 0.7-1.9). Among high-dose proton pump inhibitor users (ie, > or =1.5 defined daily doses/day), there was a nonstatistically significant trend toward an increased risk with increasing duration of use (test for trend, P = .2). However, patients with pernicious anemia were not at increased risk for colorectal cancer (adjusted odds ratio, 0.9; 95% confidence interval, 0.6-1.3).Conclusions Long-term proton pump inhibitor therapy at a regular dose is not associated with a significantly increased risk of colorectal cancer.
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Many studies over the years have not found a direct correlation between PPI use in clinical practice and an increased risk of CRC.
“Nevertheless, it is fundamental to highlight that many studies over the years have not found a direct correlation between PPI use in clinical practice and an increased risk of CRC[154-156].”
From Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified (2019) · cites this paper as [154]
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Self-citationIs There a Dark Side to Long-term Proton Pump Inhibitor Therapy?
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“However, 2 recent and independent case–control studies provide no evidence for this.(11,12) The first(11) utilized the UK General Practice Research Database (UKGPRD).”
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“Ethical approval for all observational research using GPRD data has been obtained from a multicentre research ethics committee.”
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Proton pump inhibitors and risk of periampullary cancers—A nested case–control study
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“(29) However, three large case–control studies failed to identify a positive correlation between the use of PPIs and the risk of developing colon cancer.(30-32) Regarding liver tumors, one recent study from the US veterans database revealed that PPI use is associated with an increased risk of cirrhosis, hepatic decomp…”
BackgroundGastrin increases its own synthesis in gastrointestinal cancer cells via the CCK2 receptor
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“The resultant increased production of non-amidated forms of gastrin (Ggly) may explain the sustained increase in circulating gastrins in patients with colorectal cancer (CRC).”
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“Eventually, 22 eligible articles were included in our analysis (Garcia Rodriguez et al., 2006; Robertson et al., 2007; Yang et al., 2007; Tamim et al., 2008; van Soest et al., 2008; Chubak et al., 2009; Poulsen et al., 2009; Lai et al., 2013; Hwang et al., 2017; Wennerström et al., 2017; Cheung et al., 2018; Niikura e…”
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“Pantoprazole among PPIs including omeprazole, lansoprazole, and rabeprazole, was chosen after a preliminary study that pantoprazole was the most stable in inhibiting proton pump activities and was purchased from Amore-Pacific Pharma (Seoul, Korea).”
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Comprehensive analysis of proton pump inhibitors and risk of digestive tract cancers
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REVIEWS IN BASIC AND CLINICAL GASTROENTEROLOGY
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Endocrine Tumors of the Pancreas and Gastrointestinal Tract
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Indications and safety of proton pump inhibitor drug use in patients with cancer
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A Retrospective Analysis of the Role of Proton Pump Inhibitors in Colorectal Cancer Disease Survival
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Neu erkannte Nebenwirkungen von Protonenpumpeninhibitoren
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Risk of Colorectal Cancer in Patients With Barrett's Esophagus: A Dutch Population-Based Study
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Influence of Proton Pump Inhibitor Use in Gastrointestinal Polyps
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“Unfortunately, these studies did not report the results of the colonoscopy examination, precancerous evaluation or the gastrin level [19,20].”
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“Furthermore, 2 large population-based case control studies concluded there was no evidence that long-term PPI therapy was associated with an increased risk of colorectal cancer.(33,34) The effect of a modified release form of a PPI on plasma gastrin levels has not been reported in the literature.”
BackgroundCirculating gastrin concentrations in patients at increased risk of developing colorectal carcinoma
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Proton pump inhibitors and odds of cholangiocarcinoma: A retrospective case‐control study
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Proton pump inhibitors are not associated with an increased risk of colorectal cancer
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Electronic Health Record Databases
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“The index dates were taken as the earliest of any of the following: i. Date of the first colorectal cancer diagnosis code (first general cancer code for those identified via algorithm 3) Copyright © 2012 John Wiley & Sons, Ltd. Pharmacoepidemiology and Drug Safety, 2012; 21: 775–783 DOI: 10.1002/pds Copyright © 2012 J…”
InfluentialAtrophic gastritis and the risk of incident colorectal cancer
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“However, based on prescription information, recent studies did not find an increased risk of colorectal cancer with PPI use, [9–12] but the duration of PPI exposures in these studies were relatively short given the long time period required for colorectal cancer to develop from a normal mucosa.”
Neu erkannte Nebenwirkungen von Protonenpumpeninhibitoren: Argumente Pro Fundoplicatio bei GERD?
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Self-citationProton pump inhibitors: use, misuse and concerns about long-term therapy
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BackgroundInhibiteurs de la pompe à protons (IPP) et cancers : une association à risques ?
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“The findings of the European studies [29,32] suggesting a potential connection between current PPI use and CRC likelihood may also support our findings.”
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“Several drugs have been identified as having the potential to reduce CRC development and improve the prognosis, such as metformin [7], statins [8], or aspirin [9]; conversely, the association between long-term use of proton pump inhibitors (PPIs) and increased CRC risk has also been reported [10].”
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“Although there is no convincing evidence that hypergastrinemia per se induces neoplasia, the possibility exists that it might accelerate the growth and invasiveness of cancer harboring its receptors [73-77].”
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Liver injury in COVID-19 patients - a multidisciplinary experience and a call for national consensus
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- Authors
- Yang, Y., Hennessy, S., Propert, K., Hwang, W., Sedarat, A., & Lewis, J. D.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Yang, Yu–Xiao
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2007-09
- Volume
- 133
- Issue
- 3
- Pages
- 748-754
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2154036780
- Cited by
- 125
- References
- 53
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 7 · 2022: 1 · 2021: 7 · 2020: 16 · 2019: 4 · 2018: 5 · 2017: 7 · 2016: 2 · 2015: 5 · 2014: 3 · 2013: 9 · 2012: 8
- FWCI
- 8.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK062978)
- Topics
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Health Sciences › Medicine › Oncology › Colorectal Cancer Screening and Detection
- Health Sciences › Medicine › Gastroenterology › Gastroesophageal reflux and treatments
- Keywords
- proton pump inhibitors, colorectal cancer, hypergastrinemia, acid suppression, long-term drug use, pernicious anemia, dose-response relationship, cancer risk
- MeSH terms
- Adenocarcinoma, Aged, Anti-Inflammatory Agents, Non-Steroidal, Aspirin, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Gastroesophageal Reflux, United Kingdom, Humans, Longitudinal Studies, Male, Middle Aged, Risk Factors, Time Factors, Colorectal Neoplasms, Case-Control Studies, Proton Pump Inhibitors
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