Reduction of Lethal Prostate Cancer Disparities in Underserved Hispanic/Latino Populations

The proposed project will advance research into the biology of lethal prostate cancer (PCa) and reduce the burden of lethal PCa health disparities in Puerto Rican Hispanic/Latino men (PR H/L) through the following aims: Aim 1: Identify the genomic alterations and mutation signatures that characterize lethal PCa in PR Hispanic/Latino (PR H/L) men. Aim 2: Studying the lethal PCa phenotype in terms of overall DNA repair capacity (DRC) levels using lymphocytes as surrogate markers to develop a potential biomarker for identifying men at high-risk. Aim 3: To increase PCa awareness and screening in PR communities with high African ancestry and high PCa mortality rates. During this funding period, the molecular analysis for 25 prostate tumors from PR H/L men was completed: WES and RNA sequencing data are available for 14 and 25 tumors, respectively. Through RNA-seq, 31 DNA repair genes whose expression correlated with that of the androgen receptor gene were identified (P < 0.0003). For Aim 2, 85 samples were analyzed for DRC values including cases and controls. Significant differences were observed when comparing cases and controls (p<0.001). When stratifying by disease aggressiveness, significant differences were observed when comparing controls with the four PCa groups (p<0.0001). Standardization for the DNA repair assay to measure homologous recombination was completed. For Aim 3, the Community Advisory Committee (CAC) was established. A manuscript with data from Aim 3 is currently under review. Several oral presentations and posters regarding the data from Aims 2 and 3 were presented at local meetings.