Haplotype analysis in carriers of the BRCA1:c.3331_3334del variant in a sample from the state of Bahia, Brazil

Abstract

Introduction: Breast cancer is the most common type of cancer among women and accounts for approximately 30% of all female cancer diagnoses. Ovarian cancer accounts for approximately 3%. It is estimated that between 5% and 10% of breast and ovarian cancer cases are related to hereditary factors. The BRCA1 gene, directly involved in DNA repair and playing a crucial role in maintaining genomic stability, is one of the genes most associated with hereditary breast cancer and ovarian cancer (HBOC) predisposition syndrome. Germline mutations in this gene can result in an average cumulative lifetime risk of 55% to 70% for developing breast cancer and approximately 39% for ovarian cancer. Objective: associating haplotypes identified in the BRCA1 gene with a possible common origin for the c.3331_3334del mutation in Bahia. Methodology: Six microsatellite markers (STRs) along chromosome 17 (THRA1, D17S1327, D17S800, D17S855, D17S1323, D17S1323) were evaluated through fragment analysis in 12 unrelated patients with HBOC. Results: A more frequent haplotype was revealed among patients, with the combination of the following alleles: THRA1-164 (83.33%), D17S800-240 (50%), D17S855-150 (58.33%), D17S1327-150 (91.67%) and D17S1323-130 (83.33%). Only marker D17S579 presented a more heterogeneous profile. However, 5 of the 12 patients (33.33%) presented the 120-bp allele. Conclusion: The presence of a common haplotype among the evaluated patients may be associated with a founder effect and may indicate a single origin for the recurrence of the BRCA1 variant: c.3331_3334del in the Bahia population. Investigation of this mutation can be considered for the implementation of mutational screening in patients suspected of having HBOC in this population.