Reduced DNA Repair Capacity in Prostate Cancer Patients: A Phenotypic Approach Using the CometChip.

Abstract

Simple SummaryProstate cancer (PCa) is the most commonly diagnosed cancer type in Hispanic men in the US. Among Hispanics, Puerto Rican (PR) men show the highest PCa-specific mortality. Various studies have shown that having low DNA repair capacity (DRC) is a significant risk factor for cancer development. The aim of this study was to evaluate variations in DRC, through the nucleotide excision repair (NER) pathway, in PR men with PCa using the CometChip. Overall, PCa cases had lower DRC than controls. When PCa cases were stratified into aggressive and indolent, controls had higher DRC than both groups. The contributions of additional factors (i.e., age and prostate-specific antigen levels) to DRC were also considered. Our data suggest that DRC levels may have the potential to discriminate between aggressive and indolent cases. Our results represent an innovative step in the development of a blood-based screening test for PCa based on DRC levels.Prostate cancer (PCa) accounts for 22% of the new cases diagnosed in Hispanic men in the US. Among Hispanics, Puerto Rican (PR) men show the highest PCa-specific mortality. Epidemiological studies using functional assays in lymphocytes have demonstrated that having low DRC is a significant risk factor for cancer development. The aim of this study was to evaluate variations in DRC in PR men with PCa. Lymphocytes were isolated from blood samples from PCa cases (n = 41) and controls (n = 14) recruited at a hospital setting. DRC levels through the nucleotide excision repair (NER) pathway were measured with the CometChip using UVC as a NER inductor. The mean DRC for controls and PCa cases were 20.66% (±7.96) and 8.41 (±4.88), respectively (p < 0.001). The relationship between DRC and tumor aggressiveness was also evaluated. Additional comparisons were performed to evaluate the contributions of age, anthropometric measurements, and prostate-specific antigen levels to the DRC. This is the first study to apply the CometChip in a clinical cancer study. Our results represent an innovative step in the development of a blood-based screening test for PCa based on DRC levels. Our data also suggest that DRC levels may have the potential to discriminate between aggressive and indolent cases.