PMID- 34908809
OWN - NLM
STAT- MEDLINE
DCOM- 20211217
LR  - 20211217
IS  - 2219-2840 (Electronic)
IS  - 1007-9327 (Print)
IS  - 1007-9327 (Linking)
VI  - 27
IP  - 44
DP  - 2021 Nov 28
TI  - Proton pump inhibitors and colorectal cancer: A systematic review.
PG  - 7716-7733
LID - 10.3748/wjg.v27.i44.7716 [doi]
AB  - 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.
CI  - (c)The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights 
      reserved.
FAU - Patel, Agastya
AU  - Patel A
AD  - Department of General, Endocrine and Transplant Surgery, Medical University of 
      Gdansk, Gdansk 80-210, Poland.
FAU - Spychalski, Piotr
AU  - Spychalski P
AD  - Department of General, Endocrine and Transplant Surgery, Medical University of 
      Gdansk, Gdansk 80-210, Poland.
FAU - Antoszewska, Magdalena
AU  - Antoszewska M
AD  - Department of Dermatology, Venereology and Allergology, Medical University of 
      Gdansk, Gdansk 80-210, Poland.
FAU - Regula, Jaroslaw
AU  - Regula J
AD  - Department of Gastroenterology, Hepatology and Oncology, Center of Postgraduate 
      Medical Education, The Maria Sklodowska-Curie National Research Institute of 
      Oncology, Warsaw 01-813, Poland.
FAU - Kobiela, Jarek
AU  - Kobiela J
AD  - Department of General, Endocrine and Transplant Surgery, Medical University of 
      Gdansk, Gdansk 80-210, Poland. kobiela@gumed.edu.pl.
LA  - eng
PT  - Journal Article
PT  - Systematic Review
PL  - United States
TA  - World J Gastroenterol
JT  - World journal of gastroenterology
JID - 100883448
RN  - 0 (Proton Pump Inhibitors)
RN  - 6804DJ8Z9U (Capecitabine)
RN  - Q573I9DVLP (Leucovorin)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Capecitabine
MH  - *Colorectal Neoplasms/drug therapy/epidemiology
MH  - Fluorouracil
MH  - Humans
MH  - Leucovorin
MH  - *Proton Pump Inhibitors/adverse effects
PMC - PMC8641055
OTO - NOTNLM
OT  - Cancer epidemiology
OT  - Capecitabine
OT  - Carcinogenesis
OT  - Colorectal cancer
OT  - Proton pump inhibitor
OT  - Translational medicine
COIS- Conflict-of-interest statement: All the authors declare that they have no 
      competing interests.
EDAT- 2021/12/16 06:00
MHDA- 2021/12/18 06:00
PMCR- 2021/11/28
CRDT- 2021/12/15 12:24
PHST- 2021/07/04 00:00 [received]
PHST- 2021/07/14 00:00 [revised]
PHST- 2021/09/08 00:00 [accepted]
PHST- 2021/12/15 12:24 [entrez]
PHST- 2021/12/16 06:00 [pubmed]
PHST- 2021/12/18 06:00 [medline]
PHST- 2021/11/28 00:00 [pmc-release]
AID - 10.3748/wjg.v27.i44.7716 [doi]
PST - ppublish
SO  - World J Gastroenterol. 2021 Nov 28;27(44):7716-7733. doi: 
      10.3748/wjg.v27.i44.7716.