Germline variants of Brazilian women with breast cancer and detection of a novel pathogenic ATM deletion in early-onset breast cancer.
Adult
Aged
Ataxia Telangiectasia Mutated Proteins
/ genetics
BRCA1 Protein
/ genetics
BRCA2 Protein
/ genetics
Brazil
/ epidemiology
Breast Neoplasms
/ epidemiology
Cohort Studies
Female
Gene Deletion
Genetic Heterogeneity
Genetic Predisposition to Disease
Genetic Testing
Germ Cells
/ pathology
Germ-Line Mutation
Humans
Middle Aged
Ovarian Neoplasms
/ epidemiology
Young Adult
ATM
BRCA1
BRCA2
Breast and ovarian cancer susceptibility
Hereditary breast and ovarian cancer (HBOC)
Journal
Breast cancer (Tokyo, Japan)
ISSN: 1880-4233
Titre abrégé: Breast Cancer
Pays: Japan
ID NLM: 100888201
Informations de publication
Date de publication:
Mar 2021
Mar 2021
Historique:
received:
26
05
2020
accepted:
16
09
2020
pubmed:
29
9
2020
medline:
7
10
2021
entrez:
28
9
2020
Statut:
ppublish
Résumé
It is estimated that 5-10% of breast cancer cases are hereditary. The identification of pathogenic germline variants allows individualized preventive health care, improvement of clinical management and genetic counseling. Studies in ethnically admixed Latin American populations have identified regions with increased frequency of deleterious variants in breast cancer predisposing genes. In this context, the Brazilian population exhibits great genetic heterogeneity, and is not well represented in international databases, which makes it difficult to interpret the clinical relevance of germline variants. We evaluated the frequency of pathogenic/likely pathogenic (P/LP) germline variants in up to 37 breast cancer predisposing genes, in a cohort of 105 breast and/or ovarian cancer Brazilian women referred to two research centers between 2014 and 2019. A total of 22 patients (21%) were found to carry P/LP variants, and 16 VUS were detected in 15 patients (14.3%). Additionally, a novel pathogenic ATM intragenic deletion was identified in an early-onset breast cancer. We also detected a BRCA1 pathogenic variant (c.5074+2T>C) in higher frequency (10×) than in other studies with similar cohorts. Our findings contribute to the characterization of the genetic background of breast cancer predisposition in the Brazilian population as a useful resource to discriminate between deleterious variants and VUS, thus enabling improvement in the preventive health care and clinical management of carriers.
Sections du résumé
BACKGROUND
BACKGROUND
It is estimated that 5-10% of breast cancer cases are hereditary. The identification of pathogenic germline variants allows individualized preventive health care, improvement of clinical management and genetic counseling. Studies in ethnically admixed Latin American populations have identified regions with increased frequency of deleterious variants in breast cancer predisposing genes. In this context, the Brazilian population exhibits great genetic heterogeneity, and is not well represented in international databases, which makes it difficult to interpret the clinical relevance of germline variants.
METHODS
METHODS
We evaluated the frequency of pathogenic/likely pathogenic (P/LP) germline variants in up to 37 breast cancer predisposing genes, in a cohort of 105 breast and/or ovarian cancer Brazilian women referred to two research centers between 2014 and 2019.
RESULTS
RESULTS
A total of 22 patients (21%) were found to carry P/LP variants, and 16 VUS were detected in 15 patients (14.3%). Additionally, a novel pathogenic ATM intragenic deletion was identified in an early-onset breast cancer. We also detected a BRCA1 pathogenic variant (c.5074+2T>C) in higher frequency (10×) than in other studies with similar cohorts.
CONCLUSIONS
CONCLUSIONS
Our findings contribute to the characterization of the genetic background of breast cancer predisposition in the Brazilian population as a useful resource to discriminate between deleterious variants and VUS, thus enabling improvement in the preventive health care and clinical management of carriers.
Identifiants
pubmed: 32986223
doi: 10.1007/s12282-020-01165-1
pii: 10.1007/s12282-020-01165-1
doi:
Substances chimiques
BRCA1 Protein
0
BRCA1 protein, human
0
BRCA2 Protein
0
BRCA2 protein, human
0
ATM protein, human
EC 2.7.11.1
Ataxia Telangiectasia Mutated Proteins
EC 2.7.11.1
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
346-354Subventions
Organisme : Conselho Nacional de Desenvolvimento Científico e Tecnológico
ID : 307611/2018-3
Organisme : Fundação de Amparo à Pesquisa do Estado de São Paulo
ID : 2013/08028-1
Organisme : INCT-CETGEN
ID : 573633/2008-8
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