Urinary PGE-M in Men with Prostate Cancer

SIMPLE SUMMARY: Elevated levels of urinary prostaglandin E metabolite (PGE-M), a marker of inflammation, have previously been associated with cancer incidence and metastasis. Studies investigating PGE-M in prostate cancer are lacking even though chronic inflammation is a candidate risk factor for the disease. We investigated the association of PGE-M with lethal prostate cancer. We measured PGE-M in the urine of men with prostate cancer and in men without prostate cancer (population controls). Our participants included African American and European American men. Because African American men die more frequently from prostate cancer than European American men, we investigated whether high PGE-M may contribute to the increased mortality among African American prostate cancer patients. We did not observe a relationship between PGE-M and prostate cancer aggressiveness or prostate cancer-specific mortality in our study population, neither in the combined cohort nor in the race/ethnicity stratified analysis. Interestingly, however, we observed a significant relationship between high PGE-M and all-cause mortality in African American men with prostate cancer. Yet, there was no association between high PGE-M and all-cause mortality when these men were regular aspirin users. ABSTRACT: Urinary PGE-M is a stable metabolite of prostaglandin E2 (PGE2). PGE2 is a product of the inflammatory COX signaling pathway and has been associated with cancer incidence and metastasis. Its 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 (AA) and European American men. We measured urinary PGE-M using mass-spectrometry. Samples were obtained from 977 cases and 1022 controls at the time of recruitment. 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 5 years was assessed with a questionnaire. Race/ethnicity was self-reported. Urinary PGE-M levels did not differ between men with prostate cancer and population-based controls. We observed no association between PGE-M and aggressive disease nor prostate-cancer-specific survival. However, we observed a statistically significant association between higher (>median) PGE-M and all-cause mortality in AA 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. 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 AA men with prostate cancer.