Prevalence of germline BRCA1/2 mutations in breast and ovarian cancer patients: A study in a reference laboratory

This retrospective study characterizes the prevalence and spectrum of (BReast CAncer gene 1 and 2 ( BRCA1/2) mutations in Saudi breast and ovarian cancer patients referred for genetic testing, to define the population-specific mutational landscape. Comprehensive molecular characterization was performed on 145 blood samples from breast and ovarian cancer patients. Statistical analyses evaluated associations between mutation status and age, with significance thresholds set at p < 0.05. The overall prevalence of germline BRCA1/2 mutations was 19.3% (28/145 samples), with BRCA1 mutations accounting for 75% and BRCA2 for 25%. The most frequent mutation was BRCA1 p.(Ser1379Ter), detected in 39.3% of positive cases. Frameshift indels (71.4%) and stop-gained variants (10.7%) were predominant. Patients under 40 years showed a significantly higher mutation rate (32.9%, P=0.034). BRCA1 mutations were more common in ovarian cancer (71.4%), while BRCA2 variants were equally distributed between breast and ovarian cancers. This study reveals a prevalence of 19.3% for germline BRCA1/2 mutations in the tested population, with BRCA1 p.(Ser1379Ter) emerging as a recurrent variant, warranting further investigation as a possible founder mutation. The findings emphasize the importance of early genetic testing, particularly in younger high-risk individuals, and contribute to our understanding of BRCA1/2 mutational patterns in breast and ovarian cancers.