Introduction: Many studies have sought to determine if higher prostate cancer (PCa) mortality in Black men is due to biological vs. socioeconomic disparities, but results are inconsistent. In an effort to identify biological differences that may be closer to the functional biology underlying the racial disparity we performed metabolomic analyses of prostatic fluid in men with vs without biochemical recurrence (BCR) in Black and White men.
Methods: Within each race group previously banked prostatic fluids from 38 PCa men with BCR were matched on age, Gleason grade group (GG), and year of prostatectomy to 38 PCa men without BCR (152 men total). For each Black matched pair, a White matched pair with similar matching factors was selected. Prostatic fluid samples, blinded to race and BCR status were sent to Metabolon Inc for global metabolomic analysis using ultrahigh performance liquid chromatography-tandem mass spectroscopy. Metabolite data were analyzed by Johns Hopkins. Metabolites that passed dimension reduction filters were evaluated using conditional logistic regression with an elastic net penalty. Pathway analysis was done with proprietary software from Metabolon Inc.
Results: 1043 metabolites were identified. In Black men 5 of the top 10 metabolites were amino acids, with only 1 lipid, while in White men 6 of the top 10 were lipids, with only 2 amino acids. There were also significant differences in metabolic pathways, with acyl carnitines and sphingolipids significantly enriched in Blacks, while Whites were significantly enriched in pregnenolone steroids and lysophospholipids. Regression modeling revealed metabolites significantly associated with BCR that differed between Black and white men. Odds ratios associated with a 50% increase in metabolite expression ranged from 0.7 to 5.5 (TABLE).
Conclusions: This is the first study to evaluate Black-White differences in metabolomics between men with and without BCR, and the first study to evaluate racial differences in PCa outcomes using prostatic fluid as the medium for metabolomic analysis. Although there are some similarities in amino acid and lipid super-pathways, there are significant differences in sub-pathways and specific metabolites. Identification of relevant pathways, if validated in larger studies, could provide clues to risk mechanisms.
Source of Funding: Patrick C. Walsh Prostate Cancer Research Fund.
5P50CA058236Specialized Program of Research Excellence (SPORE) in Prostate Cancer, National Institutes of Health
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