The deleterious association between proton pump inhibitors and prostate cancer-specific mortality - a population-based cohort study.


Journal

Prostate cancer and prostatic diseases
ISSN: 1476-5608
Titre abrégé: Prostate Cancer Prostatic Dis
Pays: England
ID NLM: 9815755

Informations de publication

Date de publication:
12 2020
Historique:
received: 23 03 2020
accepted: 30 06 2020
revised: 21 05 2020
pubmed: 10 7 2020
medline: 18 9 2021
entrez: 10 7 2020
Statut: ppublish

Résumé

Proton pump inhibitors (PPIs) are commonly prescribed medications that have been shown to have contradicting effects on cancer. We aimed to investigate the effect of pantoprazole and other PPIs on prostate cancer (PCa) specific mortality (PCSM), use of androgen deprivation therapy (ADT), and PCa diagnosis using a large Canadian population-based cohort. We identified 21,512 men aged ≥ 66, with a history of a single negative prostate biopsy and no previous use of any of the analyzed medications between 1994 and 2016. Multivariable Cox regression models with time-dependent covariates were used to assess the associations of PPIs with PCa outcomes. All models included other medications with a putative chemopreventative effect on PCa-outcomes, and were adjusted for age, rurality, comorbidity, and study inclusion year. Over a mean follow-up of 8.06 years (SD 5.44 years), 10,999 patients (51.1%) used a PPI, 5187 patients (24.1%) had PCa, 2043 patients (9.5%) were treated with ADT, and 805 patients (3.7%) died from PCa. For every 6 months of cumulative use, pantoprazole was associated with a 3.0% (95% CI 0.3-6.0%) increased rate of ADT use, while any use of other PPIs was associated with a 39.0% (95% CI 18.0-64.0%) increased risk of PCSM. No association was found with PCa diagnosis. Upon validation of the potentially negative association of PPIs with PCa, PPI use may need to be reassessed in PCa patients.

Sections du résumé

BACKGROUND
Proton pump inhibitors (PPIs) are commonly prescribed medications that have been shown to have contradicting effects on cancer. We aimed to investigate the effect of pantoprazole and other PPIs on prostate cancer (PCa) specific mortality (PCSM), use of androgen deprivation therapy (ADT), and PCa diagnosis using a large Canadian population-based cohort.
METHODS
We identified 21,512 men aged ≥ 66, with a history of a single negative prostate biopsy and no previous use of any of the analyzed medications between 1994 and 2016. Multivariable Cox regression models with time-dependent covariates were used to assess the associations of PPIs with PCa outcomes. All models included other medications with a putative chemopreventative effect on PCa-outcomes, and were adjusted for age, rurality, comorbidity, and study inclusion year.
RESULTS
Over a mean follow-up of 8.06 years (SD 5.44 years), 10,999 patients (51.1%) used a PPI, 5187 patients (24.1%) had PCa, 2043 patients (9.5%) were treated with ADT, and 805 patients (3.7%) died from PCa. For every 6 months of cumulative use, pantoprazole was associated with a 3.0% (95% CI 0.3-6.0%) increased rate of ADT use, while any use of other PPIs was associated with a 39.0% (95% CI 18.0-64.0%) increased risk of PCSM. No association was found with PCa diagnosis.
CONCLUSIONS
Upon validation of the potentially negative association of PPIs with PCa, PPI use may need to be reassessed in PCa patients.

Identifiants

pubmed: 32641738
doi: 10.1038/s41391-020-0248-9
pii: 10.1038/s41391-020-0248-9
doi:

Substances chimiques

Androgen Antagonists 0
Proton Pump Inhibitors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

622-629

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Auteurs

Hanan Goldberg (H)

Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada. gohanan@gmail.com.
Institute of Medical Science, University of Toronto, Toronto, ON, Canada. gohanan@gmail.com.
Department of Urology, SUNY Upstate Medical University, Syracuse, NY, USA. gohanan@gmail.com.
Institute for Clinical Evaluative Sciences, Toronto, ON, Canada. gohanan@gmail.com.

Faizan K Mohsin (FK)

Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.

Refik Saskin (R)

Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.

Girish S Kulkarni (GS)

Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada.
Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.

Alejandro Berlin (A)

Department of Radiation Oncology, University of Toronto; and Techna Institute, University Health Network, Toronto, ON, Canada.

Miran Kenk (M)

Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada.

Christopher J D Wallis (CJD)

Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada.
Department of Urology, Vanderbilt University Medical Center, Nashville, TN, USA.

Thenappan Chandrasekar (T)

Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.

Zachary Klaassen (Z)

Division of Urology, Department of Surgery, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Georgia Cancer Center, Augusta, GA, USA.

Olli Saarela (O)

Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.

Linda Penn (L)

Department of Medical Biophysics, University of Toronto, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Shabbir M H Alibhai (SMH)

Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Department of Medicine, University Health Network and University of Toronto, Toronto, ON, Canada.

Neil Fleshner (N)

Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada.
Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

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