Germline gene-specific associations in a large prostate cancer cohort.

5102 Background: Identification of pathogenic germline variants (PGV) in patients (pts) with prostate cancer (PC) enables precision therapy and cascade testing. Equitable advances in precision PC management require more detailed understanding of gene-level associations. Herein we describe PC gene-specific demography in a large cohort of PC pts. Methods: Germline genetic testing (GGT) (Invitae Corp.) and insurance claims (Komodo Healthcare Map) data were linked for PC pts from 2015-2023. ICD/CPT codes were used to define PC personal and family history and disease stage (early-stage = codes for active surveillance or definitive local treatment; advanced = remaining pts). PC genes analyzed were those in NCCN PC guidelines with >100 PGV+ pts: ATM, BRCA1, BRCA2, CHEK2, HOXB13 and mismatch repair (MMR) genes ( EPCAM, MLH1, MSH2, MSH6, PMS2). Two sample t-tests were used for age and chi-square tests were used for other variables, with a Bonferroni correction for post hoc analysis. Results: 14,979 pts had GGT: 68% with advanced disease (enriched for BRCA2) and 32% with early-stage. Mean diagnosis age was 64, and significantly younger for ATM/ BRCA2/ HOXB13+ pts (p<0.04) (Table). BRCA2was the most common PGV but was not enriched in any clinician-reported race/ethnicity. CHEK2/MMR+ pts were more likely to be White ( post hoc p<0.001). The Midwest had the highest frequency of PGV (12%). A lower proportion of CHEK2+ pts resided in the South ( post hoc p<0.001). 26% of PGV+ pts had documented PC family history, which was significantly associated with BRCA2/HOXB13, and negatively correlated with MMR (p<0.02 for both). Conclusions: In this cohort of ~15,000 PC pts, gene-specific associations were detected that warrant further study. Three-quarters of pts with PGV had no claims for family PC history, highlighting the importance of GGT in all pts meeting criteria, independent of family history. Further analysis of linked data will assess real-world treatment decisions and outcomes by GGT result. Table: see text