Proton Pump Inhibitors and Prostate Cancer-Specific Mortality

[pjoshea13]

A new mostly-Canadian study below [1].

"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."

"Over a mean follow-up of 8.06 years ... 51.1% used a PPI ... 24.1% had PCa ... 9.5% were treated with ADT ... 3.7% died from PCa."

"For every 6 months of cumulative use, pantoprazole was associated with a 3.0% ... increased rate of ADT use, while any use of other PPIs was associated with a 39.0% ... increased risk of {PCa-specific mortality}."

39%!!!

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/326...

Prostate Cancer Prostatic Dis

. 2020 Jul 8. doi: 10.1038/s41391-020-0248-9. Online ahead of print.

The Deleterious Association Between Proton Pump Inhibitors and Prostate Cancer-Specific Mortality - A Population-Based Cohort Study

Hanan Goldberg 1 2 3 4 , Faizan K Mohsin 5 , Refik Saskin 6 , Girish S Kulkarni 7 6 , Alejandro Berlin 8 , Miran Kenk 7 , Christopher J D Wallis 7 9 , Thenappan Chandrasekar 10 , Zachary Klaassen 11 12 , Olli Saarela 5 , Linda Penn 13 , Shabbir M H Alibhai 14 15 , Neil Fleshner 7 14

Affiliations collapse

Affiliations

1 Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada. [e-mail].

2 Institute of Medical Science, University of Toronto, Toronto, ON, Canada. [e-mail].

3 Department of Urology, SUNY Upstate Medical University, Syracuse, NY, USA. [e-mail].

4 Institute for Clinical Evaluative Sciences, Toronto, ON, Canada. [e-mail].

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

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

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

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

9 Department of Urology, Vanderbilt University Medical Center, Nashville, TN, USA.

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

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

12 Georgia Cancer Center, Augusta, GA, USA.

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

14 Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

15 Department of Medicine, University Health Network and University of Toronto, Toronto, ON, Canada.

PMID: 32641738 DOI: 10.1038/s41391-020-0248-9

Abstract

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.

[Grumpyswife]

I just recently read that use of PPI makes one more susceptible to Covid 19 as well. Can’t recall the details but omeprazole topped the list in that article.

[noahware]

As well as the association with worse COVID-19 outcomes, it appears (quite logically) that PPIs can have profound impacts on the gut microbiome.

It makes me wonder it that impact on gut biota is directly related to those worse outcomes for PC and COVID patients. I think whatever we add to (or subtract from) our dietary and supplement intake needs to be considered in the context of how it might harm or help the wide variety of species that reside in our guts.

[pjoshea13 in reply to noahware]

"Compared with non-users, those taking PPIs once a day had an odds ratio (OR) for positivity of 2.15 (95% CI 1.90-2.44) and in twice-daily users the OR rose to 3.67 (95% CI 2.93-4.60), reported Christopher V. Almario, MD, MSHPM, of Cedars-Sinai Medical Center in Los Angeles, and colleagues."

medpagetoday.com/infectious...

-Patrick

[Hidden]

If only I knew earlier!

On mid December 2019 I had gastroscopy. Dr gave me 3 months PPI that I took.

On February 2020 my PSA started an up-going trend.

Coincidence?

[MateoBeach]

I agree with Noahware. It is crazy the number of people who are put on PPIs in our culture (51% here!) We evolved over millions of years a very energy-expensive mechanism to have everything we ingest pass through a protective hydrochloric acid bath in our stomachs before it can pass into the intestines to be absorbed. Obviously this mechanism is very important to survival.

But then we subvert it with drugs like PPIs so we can eat foods that don’t actually agree with us without heartburn rather than getting the message. Misguided medicine is not smarter than Ms. Nature! Let the gut microbiology work.

[pjoshea13 in reply to MateoBeach]

"Almario and co-authors noted that previous research has indicated that an intragastric pH of less than 3 inactivates the infectivity of COVID-19's sister virus, SARS-CoV-1, while the virus survives in a more neutral pH such as that induced by PPIs. SARS-CoV-2, the COVID-19 virus, uses the abundant GI angiotensin-converting enzyme 2 receptors to rapidly replicate within enterocytes, and increases in stomach pH of more than 3 from PPIs might allow the virus to reach the GI tract more easily, leading to enteritis, colitis, and systemic spread to other organs, including the lungs."

medpagetoday.com/infectious...

-Patrick

[SeosamhM]

Another great read, Patrick, thanks. Just thinking back on the last 30 years of the blind, commercialized pushing of PPI makes me cringe. Based on your article, I did a simple search for more general clinical papers on PPI and even the neutral ones note their "controversial" use (even from the beginning)....not that this ever reached the consumer for their consideration.

[pjoshea13 in reply to SeosamhM]

My experience with PPI's goes back ~8 years. No-one told me that they could 'unmask' C-diff. I probably picked up c-diff in hospital when I had the RP. Had no issue until I started using a PPI. The C-diff led to lymphocytic colitis. No cure, but all in the past now. It was a nightmare at the time.

fda.gov/drugs/drug-safety-a...

-Patrick

[Hidden]

It gets tricky, so what should you take as gastroprotective agent if taking aspirin?

[pjoshea13 in reply to Hidden]

Take it with food?

If between meals, take with an antacid?

But I'm not a doctor, etc. etc. That's why I added the question marks. (But that's what I would do.)

-Patrick

[Hidden in reply to pjoshea13]

What about cimetidine as alternative (some take it as anti cancer drug)? would it still be a sort of PPI or not?

[pjoshea13 in reply to Hidden]

I don't know about cimetidine. The VITAL study found that "daily cimetidine use for 10 years was associated with increased risk (relative risk, 2.35 ...) compared with nonuse of any H2 blockers." [1].

It's a weak antiandrogen but increases estrogen & decreases zinc.

Would be interesting to compare risk in men who took zinc & those who did not.

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/168...