Prevalence of BRCA1/BRCA2 mutations in a Brazilian population sample at-risk for hereditary breast cancer and characterization of its genetic ancestry

Autor: Gabriela C. Fernandes, Rodrigo A.D. Michelli, Henrique C.R. Galvão, André E. Paula, Rui Pereira, Carlos E. Andrade, Paula S. Felicio, Cristiano P. Souza, Deise R.P. Mendes, Sahlua Volc, Gustavo N. Berardinelli, Rebeca S. Grasel, Cristina S. Sabato, Danilo V. Viana, José Carlos Machado, José Luis Costa, Edmundo C. Mauad, Cristovam Scapulatempo-Neto, Banu Arun, Rui M. Reis, Edenir I. Palmero
Přispěvatelé: [et. al], Universidade do Minho
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Gerontology
Heredity
Latin Americans
endocrine system diseases
DNA Mutational Analysis
Inheritance Patterns
Brca1 brca2
0302 clinical medicine
Gene Frequency
Risk Factors
Medicine
c.5266dupC prevalence in brazil
skin and connective tissue diseases
Aged
80 and over
Ovarian Neoplasms
HBOC in brazil
education.field_of_study
BRCA1 Protein
hereditary breast cancer
Middle Aged
genetic ancestry
Pedigree
3. Good health
Phenotype
Oncology
030220 oncology & carcinogenesis
Female
BRCA1/BRCA2 mutation profile in Brazil
Brazil
Research Paper
Hereditary Breast Cancer
Adult
Adolescent
Genetic genealogy
Population
Breast Neoplasms
Risk Assessment
Young Adult
03 medical and health sciences
parasitic diseases
Biomarkers
Tumor
Humans
Genetic Predisposition to Disease
education
Germ-Line Mutation
Aged
BRCA2 Protein
Science & Technology
Native american
business.industry
Cancer
medicine.disease
030104 developmental biology
Brazilian population
business
Demography
Zdroj: Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
Oncotarget
Popis: Background: There are very few data about the mutational profile of families at-risk for hereditary breast and ovarian cancer (HBOC) from Latin America (LA) and especially from Brazil, the largest and most populated country in LA. Results: Of the 349 probands analyzed, 21.5% were BRCA1/BRCA2 mutated, 65.3% at BRCA1 and 34.7% at BRCA2 gene. The mutation c. 5266dupC (former 5382insC) was the most frequent alteration, representing 36.7% of the BRCA1 mutations and 24.0% of all mutations identified. Together with the BRCA1 c. 3331_ 3334delCAAG mutation, these mutations constitutes about 35% of the identified mutations and more than 50% of the BRCA1 pathogenic mutations. Interestingly, six new mutations were identified. Additionally, 39 out of the 44 pathogenic mutations identified were not previously reported in the Brazilian population. Besides, 36 different variants of unknown significance (VUS) were identified. Regarding ancestry, average ancestry proportions were 70.6% European, 14.5% African, 8.0% Native American and 6.8% East Asian. Materials and methods: This study characterized 349 Brazilian families at-risk for HBOC regarding their germline BRCA1/BRCA2 status and genetic ancestry. Conclusions: This is the largest report of BRCA1/BRCA2 assessment in an at-risk HBOC Brazilian population. We identified 21.5% of patients harboring BRCA1/BRCA2 mutations and characterized the genetic ancestry of a sample group at-risk for hereditary breast cancer showing once again how admixed is the Brazilian population. No association was found between genetic ancestry and mutational status. The knowledge of the mutational profile in a population can contribute to the definition of more cost-effective strategies for the identification of HBOC families.
This study was partially supported by FINEP - CT-INFRA (02/2010) and FAPESP (2013/24633-2). RMR is recipient of a National Council of Technological and Scientific Development (CNPq) scholarship. RP is recipient of grant SFRH/BPD/81986/2011 from the Portuguese Foundation for Science and Technology (FCT).
Databáze: OpenAIRE
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