Statin Use Is Associated with Lower Risk of PTEN-Null and Lethal Prostate Cancer

[pjoshea13]

New Health Professionals Follow-up Study paper below [1].

"... study included 44,126 men cancer-free in 1990, followed for prostate cancer incidence through 2014, with statin use recorded on biennial questionnaires."

"During 24 years of follow-up, 6,305 prostate cancers were diagnosed and 801 (13%) were lethal (metastatic at diagnosis or metastatic/fatal during follow-up)."

"Relative to never/past use, current statin use was inversely associated with risk of lethal prostate cancer [HR, 0.76 ...] but not overall disease."

"We found a strong inverse association for risk of PTEN-null cancers (HR, 0.40 ..."

"Molecular tumor classification identified PTEN and inflammation/immune activation as potential mechanisms linking statins with lower lethal prostate cancer risk."

-Patrick

[1] clincancerres.aacrjournals....

Statin Use Is Associated with Lower Risk of PTEN-Null and Lethal Prostate Cancer

Emma H. Allott, Ericka M. Ebot, Konrad H. Stopsack, Amparo G. Gonzalez-Feliciano, Sarah C. Markt, Kathryn M. Wilson, Thomas U. Ahearn, Travis A. Gerke, Mary K. Downer, Jennifer R. Rider, Stephen J. Freedland, Tamara L. Lotan, Philip W. Kantoff, Elizabeth A. Platz, Massimo Loda, Meir J. Stampfer, Edward Giovannucci, Christopher J. Sweeney, Stephen P. Finn and Lorelei A. Mucci

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DOI: 10.1158/1078-0432.CCR-19-2853

ArticleFigures & DataInfo & Metrics PDF

Abstract

Purpose: Statins are associated with lower risk of aggressive prostate cancer, but lethal prostate cancer is understudied and contributing mechanisms are unclear. We prospectively examined statins and lethal prostate cancer risk in the Health Professionals Follow-up Study (HPFS), tested associations with molecular subtypes, and integrated gene expression profiling to identify putative mechanisms.

Experimental Design: Our study included 44,126 men cancer-free in 1990, followed for prostate cancer incidence through 2014, with statin use recorded on biennial questionnaires. We used multivariable Cox regression to examine associations between statins and prostate cancer risk overall, by measures of clinically significant disease, and by ERG and PTEN status. In an exploratory analysis, age-adjusted gene set enrichment analysis identified statin-associated pathways enriched in tumor and adjacent normal prostate tissue.

Results: During 24 years of follow-up, 6,305 prostate cancers were diagnosed and 801 (13%) were lethal (metastatic at diagnosis or metastatic/fatal during follow-up). Relative to never/past use, current statin use was inversely associated with risk of lethal prostate cancer [HR, 0.76; 95% confidence interval (CI), 0.60–0.96] but not overall disease. We found a strong inverse association for risk of PTEN-null cancers (HR, 0.40; 95% CI, 0.19–0.87) but not PTEN-intact cancers (HR, 1.18; 95% CI, 0.95–1.48; P heterogeneity = 0.01). Associations did not differ by ERG. Inflammation and immune pathways were enriched in normal prostate tissue of statin ever (n = 10) versus never users (n = 103).

Conclusions: Molecular tumor classification identified PTEN and inflammation/immune activation as potential mechanisms linking statins with lower lethal prostate cancer risk. These findings support a potential causal association and could inform selection of relevant biomarkers for statin clinical trials.

Footnotes

Note: Supplementary data for this article are available at Clinical Cancer Research Online (clincancerres.aacrjournals.....

Prior Presentation: This study was previously presented in part as a poster at the American Association for Cancer Research Prostate Cancer: Advances in Basic, Translational, and Clinical Research Meeting, Orlando, Florida (2017); at the American Urological Association Annual Meeting, San Francisco, California (2018); and at the 4th International Molecular Pathological Epidemiology meeting, Boston, Massachusetts (2018).

Clin Cancer Res 2020;XX:XX–XX

Received August 29, 2019.

Revision received October 22, 2019.

Accepted November 15, 2019.

Published first November 21, 2019.

©2019 American Association for Cancer Research.

[6357axbz]

Thanks Patrick

[LearnAll]

Thanks. Another reason to continue my berberine (metformin)

[Rfs1975 in reply to LearnAll]

What dosage of Bernadine do you take daily. I currently take 1000 to 1500 mg. I also take Red Yeast Rice 1200 mg/day.

Look forward to your feedback

[LearnAll in reply to Rfs1975]

I take the same dose. I do not have high blood sugar so 1000 mg berberine is enough for me. Red yeast rice 1200 mg a day and garlic have brought my lipids to normal levels.

[Rfs1975 in reply to LearnAll]

Thanks for the feedback. My blood glucose is also normal and also take a garlic supplements. I also include Black Seed Oil and Braggs Apple Cider vinegar

Rich

[LearnAll in reply to Rfs1975]

interesting. i take black cumin seed oil capsules too.In Middle Eastern countries, black cumin seeed is considered a very beneficial medicine.

[Garp41]

Patrick,

Any ideas which statins would be best/safest?

Doug.

[pjoshea13 in reply to Garp41]

Doug,

I favor the statins at the high end of lipophilic. I began with Simvastatin years ago based on studies. I'm sticking with it for now. Not saying it's the best.

Studies, such as there are, indicate a dosage effect, which is why I would always go with the highest tolerable dose.

Some have been advised by Dr. Myers to use a statin that is not particularly lipophilic, but I think that Myers was concerned about controling cholesterol - not PCa.

-Patrick

[PhilipSZacarias in reply to pjoshea13]

Hello Patrick, As always, thank you for posting the paper. I brought the issue of switching from rosuvastatin (Crestor), a hydrophilic statin, to a more lipophilic statin with my oncologist at Princess Margaret Hospital in Toronto, Ontario. He strongly advised me to stay on Crestor - it appears he's involved in ongoing research indicating that it performs better. There were many other things I needed to discuss during the short visit so I took it at face value - I will ask for more details next time. Rosuvastatin at 20 mg is equivalent to 80 mg of other statins, with respect to decreasing LDL. In order to improve the efficacy of the statin, I started taking dipyridamole last December - this drug appears to block the Sterol regulating end binding protein 2 (SREBP-2) pathway. Cancer cells can use this pathway to circumvent the inhibition of the mevalonate pathway. Dipyridamole also appears to modulate the immune system. Cheers, Phil

[pjoshea13 in reply to PhilipSZacarias]

Thanks Phil! -Patrick

[Hidden in reply to pjoshea13]

Low dose simvastatin aggravated my GERD / reflux symptoms. Seemed to negate the omeprazole I was taking. Switched to atorvastatin which caused no problem. I managed to twist my doctor's arm in bumping me from 10 mg (lowest dose) to 20 mg. He had a concern about knocking cholesterol too low.

[tarhoosier]

Myers prescribed simvastatin for me due to my cholesterol in the "normal" range but not "ideal" (his term). My total cholesterol was not affected by the drug much, a small decline but he was much more interested in the small particle lab number. He tried to explain it to me but I never grasped his concept. I continue now with my current MO.