Statin use & lethal PCa.

[pjoshea13]

New Health Professionals Follow-up Study (HPFS), below [1].

"Purpose:Statins are associated with lower risk of aggressive prostate cancer, but lethal prostate cancer is understudied and contributing mechanisms unclear."

"Our 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 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; ...) but not PTEN-intact cancers (HR 1.18 ...)"

{Note, PTEN is a tumor suppressor gene.}

-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

Abstract

Purpose:Statins are associated with lower risk of aggressive prostate cancer, but lethal prostate cancer is understudied and contributing mechanisms 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 exploratory analysis, age-adjusted gene set enrichment analysis identified statin-associated pathways enriched in tumor and adjacent normal prostate tissue. Results: During 24 years 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%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 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.

Received August 29, 2019.

Revision received October 22, 2019.

Accepted November 15, 2019.

Copyright ©2019, American Association for Cancer Research.

[pjoshea13]

newswise.com/articles/new-r... -Patrick

"Newswise — New research led by Queen’s University Belfast has found that men who are on statins, medicine used to lower blood cholesterol, may have a reduced risk of developing a more lethal form of prostate cancer.

The study, published today in Clinical Cancer Research, a journal of the American Association, was carried out by researchers at Queen’s University Belfast, Trinity College Dublin and the Dana-Farber/Harvard Cancer Center.

Statins are drugs that are often used to help lower cholesterol levels and can reduce the risk of heart attack, stroke and heart disease. Previous studies have suggested that statins could have a role in slowing down the growth of different types of cancers. This research specifically looked at ways statins might affect prostate cancer.

The researchers discovered that there were no differences in the overall rates of prostate cancer among men who were prescribed statins. However, men who had taken statin medicines had a 24% reduced risk of developing a more lethal type of prostate cancer when compared to men who were not.

Lead author Dr Emma Allott, from the Centre for Cancer Research and Cell Biology and the Institute for Global Food Security at Queen’s University Belfast, said: “Some prostate cancers are slow growing and will not affect the man over the course of his lifetime, but others are aggressive and often deadly. My work is to understand the biology driving these different types of prostate cancer in order to reduce the number of men who develop this lethal form of the disease.

“By studying a large group of men who had been monitored for 24 years, we were able to see the link between statin use and the prevention of lethal prostate cancer. We then looked at tissue samples from some of these men to try and understand why the statin use was having this impact.

“Although the findings are at an early stage, we were able to see that statin use may affect inflammation and immunity levels in the prostates of some men as well as having an effect on the characteristics of the tumour itself. Our findings are in agreement with some of the known biology of statins but are the first to observe these effects in prostate cancer.”

The research was funded by an international research fellowship awarded to Dr Allott by the Irish Cancer Society. Dr Allott worked in collaboration with colleagues in Ireland, Northern Ireland and the US to analyse data from a study funded by the U.S. National Cancer Institute.

Dr Robert O’Connor, Head of Research at the Irish Cancer Society, said: “Dr Allott is part of the next generation of prostate cancer research leaders, whose work is making a significant contribution to our knowledge and understanding of this challenging disease. While we are not recommending that men start taking statins unless prescribed to do so, this study provides us with building blocks to further explore how statins could be used to combat aggressive prostate cancer in the future.”"

[pjoshea13]

Hi Nala,

Recent review:

ncbi.nlm.nih.gov/pubmed/312...

-Patrick

[Hidden in reply to pjoshea13]

Hi Nalakrats and pjoshea13

I am a bit confused regarding the existence of the two CRP tests, i.e. CRP and (high sensitivity) hs CRP.

I know that the latter is more oriented towards heart disease prediction.

For PCa monitoring, is there any preference/difference. TIA

[LearnAll in reply to Hidden]

CRP measures extent of total systemic inflammation ...whereas the hs CRP fraction is specific to cardiac inflammation.

For our purpose (PCA pts) , we need to measure CRP (and not hsCRP) and try to keep CRP below 1.0 .

[Hidden in reply to LearnAll]

Thank you learnAll

[pjoshea13 in reply to Hidden]

There are a number of PCa studies that chose to use the hs-CRP test, e.g. see this Oct. paper:

ncbi.nlm.nih.gov/pubmed/315...

"Our study supports that hs-CRP including repeated measurements alone or in combination with WBC may be a useful inflammation-related biomarker for prostate cancer risk and prognosis."

I don't know the rationale.

-Patrick

[GeorgeGlass in reply to pjoshea13]

Nal, Patrick - What do you guys think about the probiotic impacts on inflammation and it's use by PCx patients like us?:

ncbi.nlm.nih.gov/pubmed/308...

[pjoshea13 in reply to GeorgeGlass]

George,

I am using low-dose Minocycline, so I'm also taking probiotics every day. I have no idea as to the effect on my inflammation markers, but a basic approach I have used since diagnosis is to take anything that may have an incremental benefit. & inflammation has long been a target for me.

-Patrick

[GeorgeGlass in reply to pjoshea13]

do you take the Minocycline for arthritis? It causes gut destruction or degradation like other antibiotics?

[pjoshea13 in reply to GeorgeGlass]

George,

Low dose for PCa:

healthunlocked.com/advanced...

-Patrick

[GeorgeGlass]

Nal, Patrick - What do you guys think about the probiotic impacts on inflammation and it's use by PCx patients like us?:

ncbi.nlm.nih.gov/pubmed/308...

[Schwah in reply to GeorgeGlass]

I’d like to hear from them also. I’d love Tall Allan, our resident skeptic, to weigh in also. I love having different perspectives so I can make informed decisions. This place is awesome for that.

Schwah