Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Zayas-Villanueva OA

PROVIDER: S-EPMC6647062 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Zayas-Villanueva Omar Alejandro OA Campos-Acevedo Luis Daniel LD Lugo-Trampe José de Jesús JJ Hernández-Barajas David D González-Guerrero Juan Francisco JF Noriega-Iriondo María Fernanda MF Ramírez-Sánchez Ilse Alejandra IA Martínez-de-Villarreal Laura Elia LE

BMC cancer 20190722 1

<h4>Background</h4>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 pa ...[more]

PMID: 31331294

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Project description:BackgroundVariants of unknown significance (VUSs) have been identified in BRCA1 and BRCA2 and account for the majority of all identified sequence alterations. Notably, VUSs occur disproportionately in people of African descent hampering breast cancer (BCa) management and prevention efforts in the population. Our study sought to identify and characterize mutations associated with increased risk of BCa at young age.MethodsIn our study, the spectrum of mutations in BRCA1 and BRCA2 was enumerated in a cohort of 31 African American women of early age at onset breast cancer, with a family history of breast or cancer in general and/or with triple negative breast cancer. To improve the characterization of the BRCA1 and BRCA2 variants, bioinformatics tools were utilized to predict the potential function of each of the variants.ResultsUsing next generation sequencing methods and in silico analysis of variants, a total of 197 BRCA1 and 266 BRCA2 variants comprising 77 unique variants were identified in 31 patients. Of the 77 unique variants, one (1.3%) was a pathogenic frameshift mutation (rs80359304; BRCA2 Met591Ile), 13 (16.9%) were possibly pathogenic, 34 (44.2%) were benign, and 29 (37.7%) were VUSs. Genetic epidemiological approaches were used to determine the association with variant, haplotype, and phenotypes, such as age at diagnosis, family history of cancer and family history of breast cancer. There were 5 BRCA1 SNPs associated with age at diagnosis; rs1799966 (P=.045; Log Additive model), rs16942 (P=.033; Log Additive model), rs1799949 (P=.058; Log Additive model), rs373413425 (P=.040 and .023; Dominant and Log Additive models, respectively) and rs3765640 (P=.033 Log Additive model). Additionally, a haplotype composed of all 5 SNPs was found to be significantly associated with younger age at diagnosis using linear regression modeling (P=.023). Specifically, the haplotype containing all the variant alleles was associated with older age at diagnosis (OR= 5.03 95% CI=.91-9.14).ConclusionsKnowing a patient's BRCA mutation status is important for prevention and treatment decision-making. Improving the characterization of mutations will lead to better management, treatment, and BCa prevention efforts in African Americans who are disproportionately affected with aggressive BCa and may inform future precision medicine genomic-based clinical studies.

Dataset Information

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

Publications

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

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