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

Introduction The 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. Methods All 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. Results We 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). Conclusions Scanning 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by Libyan Scientific Research Authority ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was granted by the Bioethics Committee of the Biotechnology Research Centre (Reference No. BEC-BTRC 03-2014; Annex I). Volunteering patients and healthy controls signed informed consent forms. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors