Open Access Research

Prevalence of the BRCA1 founder mutation c.5266dupin Brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome

Ingrid P Ewald12, Patrícia Izetti13, Fernando R Vargas45, Miguel AM Moreira56, Aline S Moreira56, Carlos A Moreira-Filho7, Danielle R Cunha8, Sara Hamaguchi8, Suzi A Camey9, Aishameriane Schmidt9, Maira Caleffi10, Patrícia Koehler-Santos12, Roberto Giugliani1112132 and Patricia Ashton-Prolla111121323*

Author Affiliations

1 Laboratório de Medicina Genômica, Centro de Pesquisa Experimental - Hospital de Clínicas de Porto Alegre. Rua Ramiro Barcelos 2350. 90035-903. Porto Alegre, RS. Brazil

2 Programa de Pós-Graduação em Medicina: Ciências Médicas, Universidade Federal do Rio Grande do Sul. Rua Ramiro Barcelos 2400, 2° andar. 90035-903. Porto Alegre, Brazil

3 Programa de Pós-Graduação em Genética de Biologia Molecular, Universidade Federal do Rio Grande do Sul. Av. Bento Gonçalves, 9500 - Prédio 43323M. 91501-970 - Caixa Postal 15053 - Porto Alegre, RS, Brasil

4 Departamento de Genética e Biologia Molecular, Centro de Ciências Biológicas e da Saúde, Universidade Federal do Estado do Rio de Janeiro. Rua Frei Caneca, 94. 20211-030 Rio de Janeiro, Brazil

5 Divisão de Genética, INCA (Instituto Nacional de Câncer). Rua André Cavalcanti, 37 - Centro 20231-050. Rio de Janeiro, Brazil

6 Laboratório de Genômica Funcional e Bioinformática, Instituto Oswaldo Cruz (IOC-FIOCRUZ), Fundação Oswaldo Cruz, Av. Brasil 4365. Pavilhão Leônidas Deane (Pav. 26) - 1° andar- sala 110 21040-900 - Rio de Janeiro, Brazil

7 Departamento de Pediatria, Faculdade de Medicina da Universidade de São Paulo. Av. Dr. Enéas Carvalho de Aguiar 647. 05403-900, São Paulo, Brazil

8 Instituto Israelita de Ensino e Pesquisa Albert Einstein. Av. Albert Einstein 627, 05651-901. São Paulo, Brazil

9 Instituto de Matemática, Universidade Federal do Rio Grande do Sul. Av. Bento Gonçalves 9500 Prédio 43-111 - Agronomia. Caixa Postal 15080, Porto Alegre, Brazil

10 Núcleo Mama Moinhos. Associação Hospitalar Moinhos de Vento. Rua Ramiro Barcelos 910, 11°. Andar. 90035-001, Porto Alegre, Brazil

11 Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre. Rua Ramiro Barcelos 2350. 90035-903. Porto Alegre, RS. Brazil

12 Departamento de Genética, Universidade Federal do Rio Grande do Sul. Av. Bento Gonçalves, 9500 - Prédio 43323. Caixa Postal 15053 - 91501-970. Porto Alegre, Brazil

13 Instituto Nacional de Genética Médica Populacional - INAGEMP. Hospital de Clínicas de Porto Alegre. Rua Ramiro Barcelos 2350. 90035-903. Porto Alegre, RS. Brazil

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Hereditary Cancer in Clinical Practice 2011, 9:12  doi:10.1186/1897-4287-9-12

Published: 20 December 2011

Abstract

About 5-10% of breast and ovarian carcinomas are hereditary and most of these result from germline mutations in the BRCA1 and BRCA2 genes. In women of Ashkenazi Jewish ascendance, up to 30% of breast and ovarian carcinomas may be attributable to mutations in these genes, where 3 founder mutations, c.68_69del (185delAG) and c.5266dup (5382insC) in BRCA1 and c.5946del (6174delT) in BRCA2, are commonly encountered. It has been suggested by some authors that screening for founder mutations should be undertaken in all Brazilian women with breast cancer. Thus, the goal of this study was to determine the prevalence of three founder mutations, commonly identified in Ashkenazi individuals in a sample of non-Ashkenazi cancer-affected Brazilian women with clearly defined risk factors for hereditary breast and ovarian cancer (HBOC) syndrome. Among 137 unrelated Brazilian women from HBOC families, the BRCA1c.5266dup mutation was identified in seven individuals (5%). This prevalence is similar to that encountered in non-Ashkenazi HBOC families in other populations. However, among patients with bilateral breast cancer, the frequency of c.5266dup was significantly higher when compared to patients with unilateral breast tumors (12.1% vs 1.2%, p = 0.023). The BRCA1 c.68_69del and BRCA2 c.5946del mutations did not occur in this sample. We conclude that screening non-Ashkenazi breast cancer-affected women from the ethnically heterogeneous Brazilian populations for the BRCA1 c.68_69del and BRCA2 c.5946del is not justified, and that screening for BRCA1c.5266dup should be considered in high risk patients, given its prevalence as a single mutation. In high-risk patients, a negative screening result should always be followed by comprehensive BRCA gene testing. The finding of a significantly higher frequency of BRCA1 c.5266dup in women with bilateral breast cancer, as well as existence of other as yet unidentified founder mutations in this population, should be further assessed in a larger well characterized high-risk cohort.

Keywords:
Hereditary breast cancer; Hereditary breast and ovarian cancer Syndrome; Founder mutations; BRCA1 gene; BRCA2 gene