Circulating metabolite biomarkers associated with prostate cancer risk in Black Americans: findings from the Southern Community Cohort Study

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BACKGROUND: Despite the importance of metabolic reprogramming in prostate cancer initiation and progression, little is known about metabolic features associated with prostate cancer risk among Black Americans. METHODS: This nested case-control study included 195 incident prostate cancer cases and 379 matched controls, focusing on Black Americans from the Southern Community Cohort Study. Using pre-diagnostic plasma samples, a global, semi-quantitative metabolomics assay was conducted. Multivariable-adjusted conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for prostate cancer risk associated with a one standard-deviation increase in log-transformed metabolite levels. RESULTS: A total of 26 metabolites were associated with incident prostate cancer at p < 0.01. Of them, seven metabolites were independently associated with prostate cancer risk after mutual adjustment, including S-adenosylhomocysteine (SAH; OR [95% CI] = 0.69 [0.55-0.88]), 14-HDoHE/17-HDoHE (1.46 [1.17-1.83]), 1-linoleoyl-GPI (18:2)* (0.73 [0.57-0.92]), Sphingomyelin (d17:1/16:0, d18:1/15:0, d16:1/17:0)* (1.28 [1.03-1.59]), Gamma-glutamyl-epsilon-lysine (1.45 [1.14-1.85]), and 2,2'-Methylenebis(6-tert-butyl-p-cresol) (0.62 [0.40-0.95]). SAH and 14-HDoHE/17-HDoHE were exclusively linked to aggressive prostate cancer, while the other five metabolites were primarily associated with non-aggressive forms. CONCLUSIONS: We found several circulating metabolites as potential biomarkers for prostate cancer risk among Black Americans. Further large-scale studies are warranted to confirm our findings and to elucidate potential mechanisms.

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