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Frequency of germline genetic variants in women with a personal or family history of breast cancer from Brazil

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Abstract

Background

About 5–10% of breast cancer cases are related to genetic and hereditary factors. The application of Next Generation Sequencing (NGS) in oncology has allowed the identification of genetic variants present in several genes related to the increased risk of breast cancer. This study aimed to determine the frequency of germline genetic variants in patients with a family and/or personal history of breast cancer.

Methods

An analysis of positive reports from NGS panels was carried out in female individuals with a personal and/or family history of breast cancer, present in the database of a private laboratory in Brazil.

Results

From about 2000 reports, 183 individuals presented 219 different germline genetic variants. The genes with the highest number of variants were BRCA2 (16.0%), ATM (15.0%) and BRCA1 (12.8%). Among the variants found, 78 were either pathogenic or probably pathogenic, accounting for 35% of all variants discovered. The gene with the highest proportion of pathogenic/probably pathogenic variants was TP53 (80%) and the most frequent pathogenic variant was also reported in this gene (c.1010G > A p.(Arg337His)). Furthermore, the study obtained a high proportion of variants of uncertain significance (VUS) (65%) and approximately 32% of the variants found were in genes of moderate penetrance.

Conclusions

Our results could improve the risk estimation and clinical follow-up of Brazilian patients with a history of breast cancer.

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Data availability

Database will be made available if required.

Code availability

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Funding

KBG is grateful to Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq for the research fellowship.

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Authors and Affiliations

  1. Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Júlia Zanon Pereira & Karina Braga Gomes

  2. Laboratório Personal, Belo Horizonte, Minas Gerais, Brazil

    Juliana Garcia Carneiro, Mariana Sousa Vieira, Bruna Mattioly Valente, Pâmella Zorzan de Oliveira, Carolina Lins Mello & Caroline Leonel Vasconcelos de Campos

  3. Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Caroline Leonel Vasconcelos de Campos

  4. Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Presidente Antônio Carlos Avenue, 6627, Pampulha, Belo Horizonte, Minas Gerais, 31270-901, Brazil

    Karina Braga Gomes

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by JZP, JGC, MSV, BMV, PZO, CLM, CLVC, KBG The first draft of the manuscript was written by JZP, CLVC, KBG. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Karina Braga Gomes.

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The study was approved by the Ethics Comitte of Federal University of Minas Gerais (CAAE- 54070121.0.0000.5149).

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Pereira, J.Z., Carneiro, J.G., Vieira, M.S. et al. Frequency of germline genetic variants in women with a personal or family history of breast cancer from Brazil. Mol Biol Rep 49, 9509–9520 (2022). https://doi.org/10.1007/s11033-022-07840-0

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