Germline variant spectrum and pragmatic family history assessment in prostate cancer: a 250-patient Turkish cohort

Germline genetic testing is increasingly incorporated into prostate cancer care, but data from underrepresented populations remain limited and optimal approaches to family history assessment are uncertain. We retrospectively evaluated 250 consecutive patients with histologically confirmed prostate adenocarcinoma who underwent germline testing using a 60-gene hereditary cancer panel. Pathogenic or likely pathogenic (P/LP) variants were identified in 34 patients (13.6%), most frequently in ATM (n = 9), BRCA2 (n = 8), and MUTYH (n = 5). P/LP variant detection was not significantly associated with age at diagnosis, metastatic disease, or ISUP grade group. In contrast, a pragmatic study-defined family history was more frequent among patients with P/LP variants than among those without such variants (89.7% vs 54.1%, p < 0.001) and remained independently associated with P/LP variant detection in multivariable analysis (adjusted OR 8.31, 95% CI 2.35–29.38; p = 0.001). Among 18 P/LP variant carriers who could be classified using both approaches, 83.3% met the study-defined family history criteria compared with 38.9% meeting National Comprehensive Cancer Network family history criteria (p = 0.008). These findings demonstrate a broad spectrum of germline P/LP variants in Turkish patients with prostate cancer and suggest that a pragmatic family history assessment may complement guideline-based approaches to germline testing.