Identifying a Recurrent BRCA1 Variant in the Qatari Population With Unique Genotype-Phenotype Correlations

Area of Science:

• Genetics and Genomics
• Oncology
• Population Health

Background:

• Hereditary Breast and Ovarian Cancer Syndrome (HBOC) is frequently caused by BRCA1 and BRCA2 gene mutations.
• This study focuses on a specific recurrent pathogenic variant in the BRCA1 gene within the Qatari population.
• Understanding genotype-phenotype correlations is crucial for managing hereditary cancer risks.

Purpose of the Study:

• To describe a common, recurrent pathogenic BRCA1 variant in native Qatari individuals.
• To investigate the unique genotype-phenotype correlations associated with this variant.
• To analyze the clinical and epidemiological data of Qatari patients with BRCA1 variants.

Main Methods:

• Retrospective review of medical records (2013-2020) for Qatari patients with BRCA1 pathogenic variants.
• Inclusion criteria: personal/family history of breast/ovarian cancer and BRCA1 pathogenic variants.
• Statistical analysis included frequencies, proportions, Kaplan-Meier curves, and log-rank tests using Stata.

Main Results:

• Identified a common recurrent pathogenic BRCA1 variant c.4787C>A p.(Ser1596Ter) in 63 Qatari individuals from 8 consanguineous families.
• The BRCA1 c.4787C>A variant is strongly associated with early-onset, triple-negative invasive ductal carcinoma (IDC) breast cancer.
• This variant demonstrated high penetrance, particularly in families with early-onset breast cancer, and was more linked to breast than ovarian cancer.

Conclusions:

• The BRCA1 c.4787C>A pathogenic variant is highly recurrent in Qatari consanguineous families and contributes to early-onset breast cancer.
• Early identification of this specific variant can significantly improve patient survival rates.
• Personalized treatment and prevention strategies can be guided by early detection of this recurrent BRCA1 variant.