Pathogenic germline variants in a racially diverse real-world cohort of prostate cancer patients.

Pathogenic germline variant (PGV) rates in cancer risk genes and their association with clinical pathological features inform genetic testing practices for prostate cancer (PCa) patients. To determine the rate of PCa risk gene PGVs in a real-world, diverse cohort of PCa patients and identify clinical predictors of carrier status. Genetic testing results for 12 PCa risk genes, clinical, pathological, and family history of cancer variables were abstracted from clinical records for 1032 PCa patients who met National Comprehensive Cancer Network (NCCN) genetic testing criteria in oncology clinics and 3602 PCa patients who underwent testing in the VA National Precision Oncology Program (VA-NPOP). Individual gene PGV rates in PCa patients were compared to cancer-free males. Statistical testing was performed by unpaired t-tests and Fisher's exact tests, corrected for multiple testing. Of 4634 PCa patients, 5.4% had PGVs in one of 12 PCa risk genes. PGVs in BRCA2 (1.7%), ATM (1.3%), CHEK2 (1.1%), Lynch genes (0.9%), and BRCA1 (0.5%) were most common. The total PGV rate was significantly higher in 2825 self-identified White versus 1527 self-identified Black PCa patients (6.3% vs 3.7%, adjp=0.0024), although rates of BRCA2 and BRCA1 PGVs were similar (1.9% vs 1.3%, adjp=0.0885 and 0.6% vs 0.5%, adjp=0.8005, respectively). PGV rates were not significantly different in 311 Hispanic compared to 4188 non-Hispanic PCa patients (3.9% vs 5.5%, adjp=1.000). In self-identified White patients, PGV rates in ATM, BRCA1, BRCA2, CHEK2 and Lynch genes were significantly higher compared to two cancer-free male cohorts. BRCA2 and Lynch genes PGV rates were significantly higher in PCa patients compared to a cancer-free control cohort in SIRE-Black men. In a multivariable logistic regression, age at initial PCa diagnosis and self-identified race were significantly associated with any PGV. In a racially diverse, real-world cohort of individuals with PCa, lower PGV rates were identified compared to prior academic cohort studies. Outside of ATM and CHEK2, PGV rates were similar across the majority of clinical and pathological groupings. Our data support NCCN guideline indicated universal genetic testing for patients with aggressive forms of PCa.