TY - JOUR
T1 - Use of aspirin and statins in relation to inflammation in benign prostate tissue in the placebo arm of the prostate cancer prevention trial
AU - Hurwitz, Lauren M.
AU - Kulac, Ibrahim
AU - Gumuskaya, Berrak
AU - Baena Del Valle, Javier A.
AU - Benedetti, Ines
AU - Pan, Fan
AU - Liu, Jun O.
AU - Marrone, Michael T.
AU - Arnold, Kathryn B.
AU - Goodman, Phyllis J.
AU - Tangen, Catherine M.
AU - Lucia, M. Scott
AU - Thompson, Ian M.
AU - Drake, Charles G.
AU - Isaacs, William B.
AU - Nelson, William G.
AU - de Marzo, Angelo M.
AU - Platz, Elizabeth A.
N1 - Funding Information:
M.T. Marrone reports grants from NCI (K99CA246097) during the conduct of the study. K.B. Arnold reports grants from Fred Hutchinson Cancer Research Center during the conduct of the study. C.G. Drake reports personal fees from AZ Medimmune, Bayer, BMS, Compugen, Ferring, F-Star, Genocea, Janssen, Kleo, Merck, Merck-Serono, Pfizer, Pierre Fabre, Roche/Genentech, Shattuck Labs, Tizona, UroGen, Werewolf, and Harpoon outside the submitted work as well as has a patent to BMS licensed. E.A. Platz reports grants from NIH and Johns Hopkins University during the conduct of the study. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
L.M. Hurwitz and M.T. Marrone were supported by NCI National Research Service Award T32 CA09314. E.A. Platz and F. Pan were supported for this work, in part, by the Johns Hopkins Discovery Award. Additional support for the investigators was from P30 CA006973. This study used data previously collected and funded by the following NIH grants: NIDDK P50 DK082998, NCI U10 CA37429, NCI UM1 CA182883, and P50 CA58236.
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1940-6207.CAPR-19-0450
DO - 10.1158/1940-6207.CAPR-19-0450
M3 - Article
C2 - 32581009
AN - SCOPUS:85100488097
VL - 13
SP - 853
EP - 861
JO - Cancer Prevention Research
JF - Cancer Prevention Research
SN - 1940-6207
IS - 10
ER -