Mitochondrial DNA copy number assessment is a potent predictor for prostate cancer in White but not Black Individuals.

Abstract

Black individuals are disproportionately burdened by prostate cancer compared to White individuals. The mitochondrion is an untapped source for prostate cancer (PCa) biomarkers, and previous work has shown altered mitochondrial DNA (mtDNA) copy number is linked to mitochondrial dysfunction and tumorigenesis. We assess whether mtDNA copy number is altered in patients with and without PCa in a racially specific manner. Circulating cell-free mtDNA copy number from plasma and mtDNA copy number from white blood cells (WBCs) were measured in 199 patients undergoing biopsy (50/50 White cases/controls and 50/49 Black cases/controls). MtDNA copy number was determined via ddPCR. Logistic regressions tested associations between mtDNA and PCa by race. The area under the curve (AUC) was compared between covariate-only models and models with mtDNA. In both plasma and WBCs, mtDNA copy number was significantly increased in cases compared to controls in White patients, but not in Black patients. Interestingly, Black controls had higher mtDNA copy number levels than White controls. Multivariable analysis revealed significant associations of Plasma mtDNA and WBC mtDNA with PCa for White patients only. Elevated mtDNA copy number was more accurate in predicting PCa in White patients than in Black patients. Higher mtDNA copy number levels were associated with PCa in both Black and White patients. Plasma mtDNA may be more accurate than WBC mtDNA in predicting PCa incidence in Black men. Overall, Black controls had higher mtDNA copy number levels than White controls, suggesting mtDNA copy number may be implicated in PCa health disparities.