Prevalence of familial BRCA1/2 mutation in four cancer types in the United Arab Emirates and of Arab Nationals

Abstract

Abstract Background/Objectives: The presence of BRCA1/2 gene mutation significantly impacts the current and future management of patients. Germline BRCA1/2 mutations are associated with hereditary breast and ovarian cancer syndrome with significant lifetime risk. These mutations can put patients at risk of other malignancies, such as prostate, pancreatic, and male breast cancer. Hence, screening of gBRCA1/2 variants in high-risk populations is recommended. Mutations in BRCA1/2 are increasingly used in patients' treatment decisions for breast, ovarian, prostate, and pancreatic cancers. PARP inhibitors have shown significant improvements in the outcome of these patients. Here, we aim to estimate the incidence and characteristics of gBRCA1/2 variants, including variants of uncertain significance (VUS) in the UAE population. Methods: A total of 443 patients (n=306 cancers and n=137 for screening) underwent gBRCA1/2 testing through whole gene sequencing on the Illumina NextSeq500 system from 2017 until December 2022. Dubai Scientific Research Ethics authorized access to patient clinical and genetic data. Results: A total of 23 pathogenic and likely pathogenic (P/LP) variants were identified in BRCA1/2 genes from 306 (7.5%) cancer patients with 17 VUS (4.9%). Another five P/LP variants were reported from the family screening cohort of 131 (3.6%), including nine VUS (6.6%). Most VUS variants were identified in the BRCA2 gene. Conclusion: The prevalence of germline BRCA1/2 mutation in four cancer types in the UAE was 7.5% and 3.6% among non-cancer patients. Genetic testing influences the treatment plan for cancer patients, and family screening could be utilized as a tool for genetic risk assessment and prevention. By providing a landscape of BRCA1/2 variants in the UAE, clinical management can be improved for the UAE population.