Systematic Reviews
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2021; 27(44): 7716-7733
Published online Nov 28, 2021. doi: 10.3748/wjg.v27.i44.7716
Proton pump inhibitors and colorectal cancer: A systematic review
Agastya Patel, Piotr Spychalski, Magdalena Antoszewska, Jaroslaw Regula, Jarek Kobiela
Agastya Patel, Piotr Spychalski, Jarek Kobiela, Department of General, Endocrine and Transplant Surgery, Medical University of Gdansk, Gdansk 80-210, Poland
Magdalena Antoszewska, Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Gdansk 80-210, Poland
Jaroslaw Regula, Department of Gastroenterology, Hepatology and Oncology, Center of Postgraduate Medical Education, The Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw 01-813, Poland
Author contributions: Patel A, Spychalski P, Regula J and Kobiela J contributed to the conceptualization; Patel A, Spychalski P and Antoszewska M curated data; Patel A, Spychalski P and Kobiela J contributed to the methodology, visualization and writing the original draft; Spychalski P, Antoszewska M, Regula J and Kobiela J contributed to the validation; Spychalski P, Regula J and Kobiela J contributed to the supervision; Kobiela J administrated the project; and all authors contributed to the formal analysis, investigation, writing the review and editing.
Conflict-of-interest statement: All the authors declare that they have no competing interests.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 checklist, and the manuscript was prepared in accordance with the PRISMA guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jarek Kobiela, MD, PhD, Assistant Professor, Department of General, Endocrine and Transplant Surgery, Medical University of Gdansk, Marii Skłodowskiej-Curie 3a, Gdansk 80-210, Poland. kobiela@gumed.edu.pl
Received: July 4, 2021
Peer-review started: July 4, 2021
First decision: July 13, 2021
Revised: July 14, 2021
Accepted: September 8, 2021
Article in press: September 8, 2021
Published online: November 28, 2021
Processing time: 143 Days and 14.7 Hours
Abstract
BACKGROUND

The use of proton pump inhibitors (PPI) is common worldwide, with reports suggesting that they may be overused. Several studies have found that PPI may affect colorectal cancer (CRC) risk.

AIM

To summarize current knowledge on the relationship between PPI and CRC from basic research, epidemiological and clinical studies.

METHODS

This systematic review was based on the patients, interventions, comparisons, outcome models and performed according to PRISMA guidelines. MEDLINE, EMBASE, Scopus, and Web of Science databases were searched from inception until May 17, 2021. The initial search returned 2591 articles, of which, 28 studies met the inclusion criteria for this review. The studies were categorized as basic research studies (n = 12), epidemiological studies (n = 11), and CRC treatment studies (n = 5). The quality of the included studies was assessed using the Newcastle-Ottawa Scale or Cochrane Risk of Bias 2.0 tool depending on the study design.

RESULTS

Data from basic research indicates that PPI do not stimulate CRC development via the trophic effect of gastrin but instead may paradoxically inhibit it. These studies also suggest that PPI may have properties beneficial for CRC treatment. PPI appear to have anti-tumor properties (omeprazole, pantoprazole), and are potential T lymphokine-activated killer cell-originated protein kinase inhibitors (pantoprazole, ilaprazole), and chemosensitizing agents (pantoprazole). However, these mechanisms have not been confirmed in human trials. Current epidemiological studies suggest that there is no causal association between PPI use and increased CRC risk. Treatment studies show that concomitant PPI and capecitabine use may reduce the efficacy of chemotherapy resulting in poorer oncological outcomes, while also suggesting that pantoprazole may have a chemosensitizing effect with the fluorouracil, leucovorin, oxaliplatin (FOLFOX) regimen.

CONCLUSION

An unexpected inhibitory effect of PPI on CRC carcinogenesis by way of several potential mechanisms is noted. This review identifies that different PPI agents may have differential effects on CRC treatment, with practical implications. Prospective studies are warranted to delineate this relationship and assess the role of individual PPI agents.

Keywords: Colorectal cancer; Proton pump inhibitor; Carcinogenesis; Cancer epidemiology; Capecitabine; Translational medicine

Core Tip: Proton pump inhibitors (PPI) are a widely, often inappropriately, used class of drugs. Through various mechanisms, they are suspected to increase the risk of gastrointestinal cancers, including colorectal cancer (CRC). The aim of this review is to summarize existing literature on the effect of PPI on CRC. The review assessed basic research studies to identify mechanisms at play in this relationship, observational studies to determine if a causal association exists between PPI use and CRC incidence, and clinical studies to examine if PPI use during chemotherapy influences treatment efficacy and oncological outcomes.