Exploring health disparities in prostate cancer through circulating tumor DNA analysis.

Abstract

1603 Background: African American men (AAM) suffer from the highest rates of prostate cancer in the world. In addition, AAM experience the highest rates of aggressive prostate cancer and prostate cancer-specific mortality of any ethnic group in the United States [1, 2]. The reasons behind the increased burden of prostate cancer poor outcomes in AAM remain unresolved. A large proportion of variation in prostate cancer mortality remains unexplained solely by epidemiologic risk factors. We investigated genomic differences between AAM and Caucasian men with metastatic castration resistant prostate cancer (mCRPC) utilizing circulating tumor DNA (ctDNA) analysis. Methods: AAM and Caucasian men with mCRPC were enrolled in this study. We collected and analyzed 88 plasma samples, including 66 from Caucasian and 22 from African American patients, with no significant age difference between the groups. The targeted sequencing libraries were prepared following the Agilent SureSelect XT HS2 target enrichment workflow coupled with the SureSelect custom prostate cancer panel (Agilent, Inc.). The final libraries were sequenced on an Illumina NextSeq 2000 to generate 150 bp paired-end reads. Results: A total of 88 men with mCRPC were enrolled. About 60% of African American patients exhibited organ metastasis at the time of diagnosis, while this proportion was 36% for Caucasian patients and they primarily reported metastasis during relapse. Analyzing 1824 variants in 138 genes meeting inclusion criteria, 281 significant mutations across 88 genes revealed racial differences. Notably, 29% of these variants were somatic. Approximately 60 cancer-related pathways, tissues, and diseases were identified from these datasets, encompassing 59 of our significant genes. Among these associated genes, the prevalence of significant variants, higher in AAM, exceeds that in Caucasians in 76% of cases. The top genes that have more contribution in considering pathways are shown (Table). Conclusions: Genomic variations were observed in ctDNA analysis between African American and Caucasian patients diagnosed with metastatic castration-resistant prostate cancer. Our findings highlight the potential inclusion of ctDNA analysis in the clinical assessment of these patients, offering valuable insights for informed therapeutic decision-making. The top genes with the most contribution to prostate-related pathways. [Table: see text]