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Cancer Prevention Research
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Research Article

Use of Aspirin and Statins in Relation to Inflammation in Benign Prostate Tissue in the Placebo Arm of the Prostate Cancer Prevention Trial

Lauren M. Hurwitz, Ibrahim Kulac, Berrak Gumuskaya, Javier A. Baena Del Valle, Ines Benedetti, Fan Pan, Jun O. Liu, Michael T. Marrone, Kathryn B. Arnold, Phyllis J. Goodman, Catherine M. Tangen, M. Scott Lucia, Ian M. Thompson, Charles G. Drake, William B. Isaacs, William G. Nelson, Angelo M. De Marzo and Elizabeth A. Platz
Lauren M. Hurwitz
1Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
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Ibrahim Kulac
2Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
3Department of Pathology, Koç University School of Medicine, Istanbul, Turkey.
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Berrak Gumuskaya
2Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
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Javier A. Baena Del Valle
2Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
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Ines Benedetti
2Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
4Department of Basic Sciences, School of Medicine, University of Cartagena, Cartagena, Colombia.
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Fan Pan
5Department of Oncology, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
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Jun O. Liu
6Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland.
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Michael T. Marrone
1Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
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Kathryn B. Arnold
7SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
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Phyllis J. Goodman
7SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
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Catherine M. Tangen
7SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
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M. Scott Lucia
8Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
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Ian M. Thompson
9CHRISTUS Santa Rosa Hospital Medical Center, San Antonio, Texas.
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Charles G. Drake
10Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.
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William B. Isaacs
5Department of Oncology, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
11Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
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William G. Nelson
2Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
5Department of Oncology, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
11Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
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Angelo M. De Marzo
2Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
5Department of Oncology, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
11Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
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Elizabeth A. Platz
1Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
5Department of Oncology, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
11Department of Urology and the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
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  • For correspondence: eplatz1@jhu.edu
DOI: 10.1158/1940-6207.CAPR-19-0450 Published October 2020
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Abstract

Aspirin and statin use may lower the risk of advanced/fatal prostate cancer, possibly by reducing intraprostatic inflammation. To test this hypothesis, we investigated the association of aspirin and statin use with the presence and extent of intraprostatic inflammation, and the abundance of specific immune cell types, in benign prostate tissue from a subset of men from the placebo arm of the Prostate Cancer Prevention Trial. Men were classified as aspirin or statin users if they reported use at baseline or during the 7-year trial. Presence and extent of inflammation were assessed, and markers of specific immune cell types (CD4, CD8, FoxP3, CD68, and c-KIT) were scored, in slides from end-of-study prostate biopsies taken irrespective of clinical indication, per trial protocol. Logistic regression was used to estimate associations between medication use and inflammation measures, adjusted for potential confounders. Of 357 men included, 61% reported aspirin use and 32% reported statin use. Prevalence and extent of inflammation were not associated with medication use. However, aspirin users were more likely to have low FoxP3, a T regulatory cell marker [OR, 5.60; 95% confidence interval (CI), 1.16–27.07], and statin users were more likely to have low CD68, a macrophage marker (OR, 1.63; 95% CI, 0.81–3.27). If confirmed, these results suggest that these medications may alter the immune milieu of the prostate, which could potentially mediate effects of these medications on advanced/fatal prostate cancer risk.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Prevention Research Online (http://cancerprevres.aacrjournals.org/).

  • Cancer Prev Res 2020;13:853–62

  • Received September 27, 2019.
  • Revision received January 3, 2020.
  • Accepted June 15, 2020.
  • Published first June 24, 2020.
  • ©2020 American Association for Cancer Research.
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Cancer Prevention Research: 13 (10)
October 2020
Volume 13, Issue 10
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Use of Aspirin and Statins in Relation to Inflammation in Benign Prostate Tissue in the Placebo Arm of the Prostate Cancer Prevention Trial
Lauren M. Hurwitz, Ibrahim Kulac, Berrak Gumuskaya, Javier A. Baena Del Valle, Ines Benedetti, Fan Pan, Jun O. Liu, Michael T. Marrone, Kathryn B. Arnold, Phyllis J. Goodman, Catherine M. Tangen, M. Scott Lucia, Ian M. Thompson, Charles G. Drake, William B. Isaacs, William G. Nelson, Angelo M. De Marzo and Elizabeth A. Platz
Cancer Prev Res October 1 2020 (13) (10) 853-862; DOI: 10.1158/1940-6207.CAPR-19-0450

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Use of Aspirin and Statins in Relation to Inflammation in Benign Prostate Tissue in the Placebo Arm of the Prostate Cancer Prevention Trial
Lauren M. Hurwitz, Ibrahim Kulac, Berrak Gumuskaya, Javier A. Baena Del Valle, Ines Benedetti, Fan Pan, Jun O. Liu, Michael T. Marrone, Kathryn B. Arnold, Phyllis J. Goodman, Catherine M. Tangen, M. Scott Lucia, Ian M. Thompson, Charles G. Drake, William B. Isaacs, William G. Nelson, Angelo M. De Marzo and Elizabeth A. Platz
Cancer Prev Res October 1 2020 (13) (10) 853-862; DOI: 10.1158/1940-6207.CAPR-19-0450
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