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

BACKGROUND: Hereditary breast and ovarian cancer syndrome (HBOC) is the most common cause of hereditary breast and ovarian cancers in Qatar and worldwide, which is caused by pathogenic variants in the BRCA1 and BRCA2 genes. The aim of this retrospective study is to describe a common recurrent pathogenic variant in the BRCA1 gene that was observed in the native Qatari population with unique genotype-phenotype correlations. METHODS: Medical records of Qatari patients (affected and unaffected) with personal and/or family history of breast and ovarian cancers who carry pathogenic/likely pathogenic variants in the BRCA1 gene were reviewed between 2013 and 2020. Epidemiological information and clinical data were reviewed, including age, gender, ethnic background, personal history of cancer, tumour characteristics, and family history. We used frequencies and proportions to describe the data and used Kaplan-Meier curves and log-rank analysis to compare survival rates. For the analysis, we used Stata Corp. 2015. Stata Statistical Software: Release 14, College Station, TX: Stata Corp. LP. ETHICAL COMPLIANCE: Ethical committee approval was obtained from Hamad Medical Corporation IRB committee (MRC-01-20-1086). RESULT: Sixty-three Qatari affected patients and unaffected individuals who carry the BRCA1 variant were included in the study. Our result confirms the presence of a common recurrent pathogenic variant c.4787C>A p.(Ser1596Ter) among Qatari patients who belong to 8 consanguineous large families, followed by c.4065_4068del p.Asn1355fs, both in BRCA1. The BRCA1 c.4787C>A variant is highly associated with early onset breast cancer, specifically invasive ductal carcinoma (IDC) triple negative breast cancer (stage I, grade III), rather than ovarian cancer. Additionally, the c.4787C>A variant was found to exhibit high penetrance in families with early-onset breast cancer. CONCLUSION: We showed that BRCA1 c.4787C>A pathogenic variant is a highly recurrent variant among Qatari consanguineous families and contributes to the early onset breast cancer in Qatar. Early identification of this variant can aid in improving patients' survival and guide early personalized treatment and prevention.