The Detection of BRCA1 and BRCA2 Mutations in Saudi Females with Breast Cancer in Al-Madinah Province by Next Generation Sequencing.

Abstract

Background: Breast cancer has the highest incidence among Saudi women and is often diagnosed at a younger age with distinct genetic features. This study aimed to determine the prevalence and mutation of germline BRCA1 and BRCA2 mutations in Saudi women in Al-Madinah Province with breast cancer.

Methods: This cross-sectional study included 54 Saudi females with a median age of 46.5 years (IQR 39.0 - 53.7 years). Genomic DNA from peripheral blood was screened using high-depth next-generation sequencing (NGS), which encompassed all coding exons and splice regions of BRCA1 and BRCA2. Variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Clinical information, such as age at diagnosis, cancer subtype, staging, treatment response, and overall survival, was collected from patients' medical files to assess them against mutation status.

Results: Pathogenic or likely pathogenic BRCA variants were found in eight patients (14.8%): five had BRCA1 mutations (62.5%), four of which were pathogenic variants including a large exon 16 deletion in one patient and one was likely a pathogenic variant. Three patients had BRCA2 mutations (37.5%); all of which were pathogenic variants. Most mutation carriers (62.5%) developed the disease at a relatively young age, particularly in BRCA2 carrier ER-positive patients, although the difference between carriers and non-carriers was not statistically significant (p = 0.6). Carriers were significantly more likely to have a positive family history (p = 0.001). The mortality rate was higher in carriers (25%) than in non-carriers (2.2%); however, this difference was statistically non-significant (p = 0.05), a finding that may be related to the small sample size.

Conclusions: Mutations of BRCA1 and BRCA2 were detected; the prevalence was 14.8%. These mutations are associated with a relatively young age at diagnosis, a positive family history, and a lower survival rate. The findings highlight the need for robust BRCA mutation screening and genetic counseling for female breast cancer patients to enable appropriate risk assessment and clinical intervention.