Germline pathogenic variants associated with prostate cancer susceptibility in a Spanish cohort: emergence of new key players.

Germline pathogenic variants in predisposition genes (BRCA2, ATM, TP53, PALB2)

Prostate cancer is among the most heritable common malignancies, yet germline data in the Spanish population are limited. The authors retrospectively analysed 360 patients referred for genetic counselling using a 13-gene predisposition panel. A germline pathogenic variant was carried by 6.4% of patients. BRCA2 and ATM were the most frequently mutated genes (1.67% each), significantly enriched versus controls; TP53 and PALB2 were also significantly associated with risk. The best predictors of carrier status were high-risk or metastatic disease, age under 60 years, and family history of hereditary breast/ovarian or Lynch-spectrum tumours.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

This cohort suggests an unexpected role for TP53 and PALB2 in prostate cancer susceptibility, while confirming BRCA2 and ATM and questioning BRCA1. Practically, targeting germline testing to younger patients with non-low-risk disease and suggestive family history optimises yield. These associations, in 360 patients from a single population, require replication before expanding prostate panels.

Analysis by Dr Thibaut Benquey