Proton pump inhibitors and all-cause mortality in colorectal cancer

Abstract Proton pump inhibitors (PPIs) are commonly prescribed medications, but their relationship to mortality in colorectal cancer (CRC) remains poorly understood. This study aims to evaluate the association between PPI use and all-cause mortality IN newly diagnosed CRC. This retrospective cohort...

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Main Authors: Arunkumar Krishnan, Carolin V Schneider, Kunal C Kadakia, Declan Walsh, Saleh A. Alqahtani
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-05570-4
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author Arunkumar Krishnan
Carolin V Schneider
Kunal C Kadakia
Declan Walsh
Saleh A. Alqahtani
author_facet Arunkumar Krishnan
Carolin V Schneider
Kunal C Kadakia
Declan Walsh
Saleh A. Alqahtani
author_sort Arunkumar Krishnan
collection DOAJ
description Abstract Proton pump inhibitors (PPIs) are commonly prescribed medications, but their relationship to mortality in colorectal cancer (CRC) remains poorly understood. This study aims to evaluate the association between PPI use and all-cause mortality IN newly diagnosed CRC. This retrospective cohort study utilized electronic medical records from a network comprising over 80 million patients across 57 healthcare organizations in the USA. We identified adult patients with a first-time CRC diagnosis between January 1, 2010, and December 31, 2022, ensuring at least one year of follow-up. Patients were classified as new users or non-users of PPIs at the time of CRC diagnosis. A lag time of 6 months was adopted to minimize protopathic bias. The primary outcome was all-cause mortality. Patients in the study group were matched with patients controls by using 1:1 propensity matching. The analysis included 252,022 patients (126,011 PPI users and 126,011 non-users) matched on propensity scores. PPI users had a higher mortality risk at 1 year (HR = 1.42), 2 years (HR = 1.44), and over the entire follow-up period (HR = 1.40). Sensitivity analyses, which excluded early outcomes, and ancillary analyses, which compared to those on histamine-2 receptor antagonists, confirmed the robustness of these results. Even for former PPI users, the all-cause mortality HR was 1.39. PPI use was associated with an increased risk of all-cause mortality in CRC patients. These findings highlight the need for further research to explore the underlying mechanisms and clinical implications of PPI use in this population. The study indicates that PPIs are associated with increased all-cause mortality in CRC. This highlights the need for careful consideration when prescribing PPIs to this population.
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spelling doaj-art-ff66a6afb36a4920988bf4b20eefbb112025-08-20T04:01:26ZengNature PortfolioScientific Reports2045-23222025-07-011511910.1038/s41598-025-05570-4Proton pump inhibitors and all-cause mortality in colorectal cancerArunkumar Krishnan0Carolin V Schneider1Kunal C Kadakia2Declan Walsh3Saleh A. Alqahtani4Department of Supportive Oncology, Atrium Health Levine CancerDepartment of Medicine III, Gastroenterology, Metabolic Diseases, and Intensive Care, University Hospital RWTH AachenDepartment of Supportive Oncology, Atrium Health Levine CancerDepartment of Supportive Oncology, Atrium Health Levine CancerOrgan Transplant Center of Excellence, King Faisal Specialist Hospital & Research CenterAbstract Proton pump inhibitors (PPIs) are commonly prescribed medications, but their relationship to mortality in colorectal cancer (CRC) remains poorly understood. This study aims to evaluate the association between PPI use and all-cause mortality IN newly diagnosed CRC. This retrospective cohort study utilized electronic medical records from a network comprising over 80 million patients across 57 healthcare organizations in the USA. We identified adult patients with a first-time CRC diagnosis between January 1, 2010, and December 31, 2022, ensuring at least one year of follow-up. Patients were classified as new users or non-users of PPIs at the time of CRC diagnosis. A lag time of 6 months was adopted to minimize protopathic bias. The primary outcome was all-cause mortality. Patients in the study group were matched with patients controls by using 1:1 propensity matching. The analysis included 252,022 patients (126,011 PPI users and 126,011 non-users) matched on propensity scores. PPI users had a higher mortality risk at 1 year (HR = 1.42), 2 years (HR = 1.44), and over the entire follow-up period (HR = 1.40). Sensitivity analyses, which excluded early outcomes, and ancillary analyses, which compared to those on histamine-2 receptor antagonists, confirmed the robustness of these results. Even for former PPI users, the all-cause mortality HR was 1.39. PPI use was associated with an increased risk of all-cause mortality in CRC patients. These findings highlight the need for further research to explore the underlying mechanisms and clinical implications of PPI use in this population. The study indicates that PPIs are associated with increased all-cause mortality in CRC. This highlights the need for careful consideration when prescribing PPIs to this population.https://doi.org/10.1038/s41598-025-05570-4All-cause mortalityCancerCarcinomaColorectal CancerH2RAHistamine-2 receptor antagonists
spellingShingle Arunkumar Krishnan
Carolin V Schneider
Kunal C Kadakia
Declan Walsh
Saleh A. Alqahtani
Proton pump inhibitors and all-cause mortality in colorectal cancer
Scientific Reports
All-cause mortality
Cancer
Carcinoma
Colorectal Cancer
H2RA
Histamine-2 receptor antagonists
title Proton pump inhibitors and all-cause mortality in colorectal cancer
title_full Proton pump inhibitors and all-cause mortality in colorectal cancer
title_fullStr Proton pump inhibitors and all-cause mortality in colorectal cancer
title_full_unstemmed Proton pump inhibitors and all-cause mortality in colorectal cancer
title_short Proton pump inhibitors and all-cause mortality in colorectal cancer
title_sort proton pump inhibitors and all cause mortality in colorectal cancer
topic All-cause mortality
Cancer
Carcinoma
Colorectal Cancer
H2RA
Histamine-2 receptor antagonists
url https://doi.org/10.1038/s41598-025-05570-4
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AT kunalckadakia protonpumpinhibitorsandallcausemortalityincolorectalcancer
AT declanwalsh protonpumpinhibitorsandallcausemortalityincolorectalcancer
AT salehaalqahtani protonpumpinhibitorsandallcausemortalityincolorectalcancer