Prostate cancer (PCa) remains one of the most prevalent malignancies among men worldwide, with both genetic and environmental factors contributing to its pathogenesis. Among hereditary factors, mutations in the BRCA1 (BReast CAncer gene 1) tumor suppressor gene have been increasingly recognized as significant risk modifiers for aggressive prostate cancer. The BRCA1 protein plays a crucial role in DNA repair mechanisms, particularly in homologous recombination repair (HRR), and its dysfunction leads to genomic instability and oncogenic transformation. Given the growing emphasis on precision oncology, molecular genetic testing for BRCA1 mutations has become essential for identifying high-risk patients who may benefit from targeted therapies, such as PARP inhibitors, and more aggressive surveillance protocols.
This study aimed to investigate the frequency and spectrum of BRCA1 mutations in a cohort of prostate cancer patients using real-time polymerase chain reaction (PCR).

The study included 282 patients with histologically confirmed prostate cancer were enrolled. Genomic DNA was extracted from peripheral blood samples using standardized commercial kits, followed by real-time PCR amplification and mutation detection using allele-specific probes.

The analysis revealed BRCA1 pathogenic variants in 22 patients (7.8%), underscoring the relevance of genetic screening in this population. The most frequently detected mutation was c.5266dup (p.Gln1756Profs), a frameshift variant leading to a truncated non-functional protein, found in 14 patients (5.0%). This mutation is a well-documented founder variant in certain populations and has been associated with increased cancer aggressiveness. The second most common variant was c.181T>G (p.Cys61Gly), a missense mutation disrupting the BRCA1 protein's zinc-binding RING domain, detected in 5 patients (1.8%). This domain is critical for BRCA1's E3 ubiquitin ligase activity and interaction with BARD1, and its impairment compromises DNA damage response. Additionally, c.4035del (p.Glu1346fs), another frameshift mutation leading to protein truncation, was identified in 3 patients (1.1%).

These findings suggest that BRCA1 mutations contribute to prostate cancer susceptibility and may correlate with more aggressive disease phenotypes. Given the role of BRCA1 in maintaining genomic integrity, its loss-of-function mutations could lead to increased tumor mutational burden and therapeutic vulnerabilities, such as sensitivity to platinum-based chemotherapy or PARP inhibition. The relatively high prevalence of BRCA1 alterations (7.8%) in this cohort highlights the potential clinical utility of genetic testing in prostate cancer management. Identifying these mutations could facilitate early intervention, familial risk assessment, and personalized treatment strategies, particularly in patients with advanced or hereditary forms of the disease.
However, further large-scale multicenter studies are needed to validate these findings and explore the correlation between specific BRCA1 variants and clinical outcomes, including response to targeted therapies. Additionally, expanding genetic screening to include other homologous recombination repair genes (e.g., BRCA2, ATM, PALB2) could provide a more comprehensive risk assessment.

In conclusion, this study demonstrates that BRCA1 mutations are present in a clinically significant subset of prostate cancer patients, reinforcing the importance of integrating molecular diagnostics into routine clinical practice. Future research should focus on the functional impact of these mutations, their prognostic significance, and their implications for emerging treatment paradigms in precision oncology.