DNA Repair Capacity and Clinicopathological Characteristics in Puerto Rican Hispanic/Latino Patients with Metastatic Castration-Resistant Prostate Cancer

Prostate cancer (PCa) accounts for 22% of the new cases diagnosed in Hispanic/Latino (H/L) men in the US. PCa has the highest incidence (38.3%) and mortality (16.4%) among all types of cancer diagnosed in Puerto Rico. We previously showed that PCa patients (n=41) have a significant reduction of 59% in their levels of DNA repair capacity (DRC) when compared to controls (n=14). This study aimed to evaluate DRC levels through the nucleotide excision repair (NER) pathway for the first time in 16 Puerto Rican H/L men with metastatic castrate-resistant PCa (mCRPCa) while establishing comparisons with controls and PCa patients with indolent and aggressive disease. Blood samples and clinicopathological data from PCa cases (n=71) and controls (n=25) were evaluated. PCa cases were stratified into mCRPCa (n=16), aggressive (n=31), and indolent (n=24). DRC levels through NER were measured in lymphocytes with the CometChip assay. The stratification by Gleason Score (GS) was: GS6 (n=7), GS7 (n=23), GS≥8 (n=20), and mCRPCa patients (n=16). Significant statistical differences were found when comparing the DRC values of the controls with any other of the four PCa patient groups. mCRPCa patients had the lowest mean DRC level of all four patient groups studied. The mean DRC level of mCRPCa patients was 6.65%, and compared to the controls, this represented a statistically significant reduction of 62% (p<0.0001). Further analysis was performed to evaluate the contributions of age, anthropometric measurements, and prostate-specific antigen (PSA) levels to the DRC. Kaplan-Meier curves of mCRPCa revealed that survival probability decreased by approximately 50% by 30 months. This pilot study uses a blood-based phenotypic assay to present the first report of mCRPCa in Puerto Rican men and at a global level of DRC levels of mCRPCa patients.