Journal Article

Analysis of the pathogenic variants of BRCA1 and BRCA2 using next-generation sequencing in women with familial breast cancer: a case–control study

Lugo-Trampe, José de Jesús, Noriega-Iriondo, María Fernanda, Zayas-Villanueva, Omar Alejandro, González-Guerrero, Juan Francisco, Martínez-de-Villarreal, Laura Elia, Hernández-Barajas, David, Ramírez-Sánchez, Ilse Alejandra, Campos-Acevedo, Luis Daniel

2019

Overview

Background Pathogenic variants (PVs) of BRCA genes entail a lifetime risk of developing breast cancer in 50–85% of carriers. Their prevalence in different populations has been previously reported. However, there is scarce information regarding the most common PVs of these genes in Latin-Americans. This study identified BRCA1 and BRCA2 PV frequency in a high-risk female population from Northeastern Mexico and determined the association of these mutations with the patients’ clinical and pathological characteristics. Methods Women were divided into three groups: aged ≤ 40 years at diagnosis and/or risk factors for hereditary breast cancer ( n  = 101), aged > 50 years with sporadic breast cancer ( n  = 22), and healthy women ( n  = 72) . Their DNA was obtained from peripheral blood samples and the variants were examined by next-generation sequencing with Ion AmpliSeq BRCA1 and BRCA2 Panel using next-generation sequencing. Results PVs were detected in 13.8% group 1 patients ( BRCA1 , 12 patients; BRCA2 , 2 patients). Only two patients in group 2 and none in group 3 exhibited BRCA1 PVs. Variants of uncertain significance were reported in 15.8% patients ( n  = 16). In group 1, patients with the triple-negative subtype, PV frequency was 40% (12/30). Breast cancer prevalence in young women examined in this study was higher than that reported by the National Cancer Institute Surveillance, Epidemiology (15.5% vs. 5.5%, respectively). Conclusions The detected BRCA1 and BRCA2 PV frequency was similar to that reported in other populations. Our results indicate that clinical data should be evaluated before genetic testing and highly recommend genetic testing in patients with the triple-negative subtype and other clinical aspects.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Adult / Biomedical and Life Sciences / Biomedicine / BRCA mutations / BRCA1 and BRCA2 genes / BRCA1 Protein - genetics / BRCA2 Protein - genetics / Breast cancer / Breast Neoplasms - genetics / Cancer genetics / Cancer Research / Case-Control Studies / DNA sequencing / Epidemiology / Exons - genetics / Familial diseases / Female / Genes / Genes, BRCA1 / Genes, BRCA2 / Genetic aspects / Genetic Loci / Genetic Testing / Genetics / genomics and epigenetics / Germ-Line Mutation / Health aspects / Health Promotion and Disease Prevention / Hereditary / High-Throughput Nucleotide Sequencing / Humans / Medicine/Public Health / Mexico / Middle Aged / Mutation Rate / Oncology / Pathogenic variant / Research Article / Risk factors / Surgical Oncology / Triple-negative subtype / Women / Young women