Abstract
Background: Chronic inflammation has been implicated in prostate cancer etiology and progression. The pro-inflammatory cyclooxygenase (COX) pathway, where arachidonic acid is converted to bioactive prostaglandins and eicosanoids via the COX1 and COX2 enzymes, has been linked to elevated systemic inflammation. Urinary PGE-M is a stable and measurable metabolite of prostaglandin E2 (PGE2). PGE2 is a product of the inflammatory COX signaling pathway and elevated levels have been associated with risk of cancer in many sites including colorectal and gastric cancers. PGE2 synthesis can be inhibited by aspirin. We investigated the association of PGE-M with lethal prostate cancer in a case-control study of African American and European American men. Identifying PGE-M as a novel marker of aggressive disease would have importance for high risk groups like men of African descent who experience a disproportionately high burden of prostate cancer lethality. Methods: We measured urinary PGE-M using mass-spectrometry. Samples were obtained from 977 cases and 1022 controls at time of recruitment. For analysis, we assessed PGE-M as either a continuous measure or assigned PGE-M values to quartiles and median with cutoff points determined using the distribution of PGE-M values among all controls. We applied multivariable logistic and Cox regression modeling to examine associations of PGE-M with prostate cancer and participant survival. Median survival follow-up was 8.4 years with 246 deaths among cases. Self-reported aspirin use over the past five years was assessed with a questionnaire. Race/ethnicity was self-reported. Results: Urinary PGE-M levels did not differ between men with prostate cancer and population-based controls. We report a lack of robust PGE-M inhibition in both cases and controls who reported aspirin use in our study. We observed no association between PGE-M and aggressive disease as defined by the National Comprehensive Cancer Network risk score. We also observed no association between PGE-M and prostate cancer-specific survival. However, we observed a statistically significant association between higher (> median) PGE-M and all-cause mortality in African American cases who did not regularly use aspirin (HR = 2.04, 95% CI 1.23-3.37). Among cases, who reported using aspirin, there was no association. Conclusions: Our study does not support a meaningful association between urinary PGE-M and prostate cancer. Moreover, PGE-M levels were not associated with aggressive prostate cancer. However, the observed association between elevated PGE-M and all-cause mortality in AA non-aspirin users reinforces the potential benefit of aspirin to reduce mortality among African American men with prostate cancer.
Citation Format: Maeve Kiely, Ginger L. Milne, Tsion Z. Minas, Tiffany H. Dorsey, Wei Tang, Cheryl J. Smith, Francine Baker, Christopher A. Loffredo, Clayton Yates, Michael B. Cook, Stefan Ambs. Association of urinary PGE-M with all-cause mortality in men with prostate cancer is influenced by aspirin use [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-168.