Racial disparities and shared genomic drivers in prostate cancer.

Abstract

e17112 Background: Prostate cancer (PC) is characterized by significant genomic heterogeneity, which drastically impacts its clinical course and therapeutic outcomes. It is historically observed that race influences clinical outcome in PC, with significant disparities between white and black communities. These disparities can be partially attributed to biological and genomic differences. This elucidates the differences in genomic profiling between these groups to identify molecular pathways affecting PC progression and prognosis. Methods: Data analyzed from the Memorial Sloan Kettering Cancer Center cBioPortal (2021 and 2024) included genomic profiles and clinical outcomes for 1,497 White and 130 Black prostate cancer (PC) patients. These profiles included survival statistics, copy number alteration, and mutational status. Prognostic implications of key genomic drivers were assessed using Kaplan-Meier survival analysis and Cox proportional hazards modeling, performed with R version 4.4.2. Results: Genomic alterations revealed both shared and distinct patterns across racial groups. TP53 mutations were common in both cohorts, observed in 32% of White patients and 20% of Black patients. Similarly, FOXA1 mutations co-occurred with androgen receptor (AR) amplifications in both groups, underscoring the role of androgen-driven tumor biology as a shared hallmark of prostate cancer. Distinct differences emerged in the frequency of other alterations. White patients exhibited higher rates of PTEN deletions (23%) and BRCA2 mutations (8%), suggesting a pronounced reliance on DNA repair deficiencies. In contrast, Black patients showed a stronger proliferation-driven molecular signature, with increased mutations in chromatin modifiers such as RECQL4 (12%) and CDK12 (12%). Clinically, Black patients presented with significantly higher PSA levels at diagnosis (165 ng/mL vs. 87 ng/mL; p < 0.001) and were diagnosed at younger ages (mean 62 years vs. 66 years; p < 0.001). Conclusions: This study highlights both race-specific and shared genomic mechanisms underlying prostate cancer. While androgen-driven pathways are predominant in both groups, White patients exhibit a greater prevalence of DNA repair deficiencies, whereas Black patients show a stronger proliferation-driven molecular profile. These findings emphasize the need for tailored treatment strategies, comprehensive genomic profiling, and greater Black representation in studies to address disparities and optimize outcomes for all patients.