Investigation of BRCA1 exon 11 genetic variations in breast cancer among Libyan women

Abstract

AbstractIntroductionThe majority of hereditary breast and ovarian cancers are associated with mutations in two genes, breast cancer type 1 and 2 susceptibility genes (BRCA1 and BRCA2). Here, we describe for the first time analysis of BRCA1 exon 11 in 48 Libyan breast cancer patients with a family history of cancer.MethodsAll patients had a family history of cancer and were included in the study only if they have a family history of breast or ovarian cancer, male breast cancer, or triple negative tumors. PCR was performed using specific primer pairs spanning BRCA1 exon 11 followed by Sanger sequencing. Genetic analysis was done using Sequencher® 5.1.ResultsWe identified 12 genetic variants in BRCA1 exon 11. Three variants were novel (c.1019T>C, c.2363T>G, and c.3192T>C). c.2363T>G was predicted by SIFT as damaging. Six variants were of unknown significance (c.918T>C, c.1853G>C, c.1886G>A, c.2215A>G, c.2612C>T, c.3113A>C and c.3784T>C), and 3 were classified as benign in ClinVar database (c.918T>C, c.2082C>T and c.2311T>C).ConclusionsScanning of the entire BRCA1 is needed to identify any associated deleterious mutations. Although the clinical importance of unclassified variants is unknown, the association of certain variants with deleterious mutations and contralateral breast cancer warrants genetic testing and counseling in the Libyan population.