Mitochondrial DNA Copy-Number Assessment Is a Potent Predictor for Prostate Cancer in White but Not Black Individuals

Black individuals are disproportionately burdened by prostate cancer compared with White individuals. The mitochondrion is an untapped source for prostate cancer biomarkers, and previous work has shown that 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 prostate cancer in a racially specific manner. Circulating cell-free mtDNA copy number from plasma and mtDNA copy number from white blood cells (WBC) were measured in 199 patients undergoing biopsy (50:50 White cases/controls and 50:49 Black cases/controls). mtDNA copy number was determined via Droplet Digital PCR. Logistic regressions tested associations between mtDNA and prostate cancer by race. The 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 with 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 prostate cancer for White patients only. Elevated mtDNA copy number was more accurate in predicting prostate cancer in White patients than in Black patients. Higher mtDNA copy number levels were associated with prostate cancer in both Black and White patients. Plasma mtDNA may be more accurate than WBC mtDNA in predicting prostate cancer incidence in Black men. Overall, Black controls had higher mtDNA copy number levels than White controls, suggesting mtDNA copy number may be implicated in prostate cancer health disparities.

Our study shows that mtDNA copy number is a significant predictor of prostate cancer in White individuals, suggesting its potential use in early detection and prevention strategies. The absence of this association in Black individuals highlights the need for race-specific biomarkers in prostate cancer prevention efforts.