Pathogenic Germline Variants in a Racially Diverse Real-World Cohort of Patients With Prostate Cancer

Pathogenic germline variant (PGV) rates in cancer risk genes and their association with clinicopathologic features inform genetic testing practices for patients with prostate cancer (PCa). In this study, we determined the rate of PGVs in PCa risk genes in a real-world, diverse cohort of patients with PCa and identified clinical predictors of carrier status.

Genetic testing results for 12 PCa risk genes, along with clinical, pathologic, and family history variables, were abstracted from 1,032 patients with PCa who met NCCN genetic testing criteria in oncology clinics, and 3,602 patients with PCa who underwent testing through the VA National Precision Oncology Program. Individual gene PGV rates in patients with PCa were compared with those in individuals assigned male at birth who were cancer-free. Statistical analyses were performed using unpaired t tests and Fisher exact tests.

Among 4,634 patients with PCa, 5.4% had PGVs, with BRCA2 (1.7%), ATM (1.3%), and CHEK2 being the most common. The total PGV rate was significantly higher in 2,825 self-identified White and 1,527 self-identified Black patients (6.3% vs 3.7%; Padjusted=.0024), although rates of BRCA2 and BRCA1 PGVs were similar (1.9% vs 1.3%; Padjusted=.0885 and 0.6% vs 0.5%; Padjusted=.8005, respectively). PGV rates did not differ significantly between 311 self-identified Hispanic and 4,188 self-identified non-Hispanic patients (3.9% vs 5.5%; Padjusted=1.000). In self-identified White and Black patients, PGV rates in BRCA2 and Lynch syndrome genes (MLH1, MSH2, MSH6, PMS2) were significantly higher compared with a cancer-free cohort of individuals assigned male at birth. In a multivariable logistic regression, age at initial PCa diagnosis and self-identified race were significantly associated with the presence of any PGV. In this racially diverse, real-world cohort of individuals with advanced PCa meeting NCCN testing criteria, the overall PGV rate was approximately 5%. Outside of ATM and CHEK2, PGV rates were similar across self-identified race, self-identified ethnicity, and clinical stage.

These data support NCCN Guideline-recommended universal genetic testing for patients with aggressive PCa.