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Prevalence of the BRCA1 founder mutation c.5266dupin Brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome |
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| Authors: | Ingrid P Ewald Patrícia Izetti Fernando R Vargas Miguel AM Moreira Aline S Moreira Carlos A Moreira-Filho Danielle R Cunha Sara Hamaguchi Suzi A Camey Aishameriane Schmidt Maira Caleffi Patrícia Koehler-Santos Roberto Giugliani Patricia Ashton-Prolla |
| Institution: | 1. Laboratório de Medicina Gen?mica, Centro de Pesquisa Experimental - Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 90035-903, Porto Alegre, RS, Brazil 2. Programa de Pós-Gradua??o 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-Gradua??o em Genética de Biologia Molecular, Universidade Federal do Rio Grande do Sul, Av. Bento Gon?alves, 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. Divis?o de Genética, INCA (Instituto Nacional de Cancer), Rua André Cavalcanti, 37 - Centro, 20231-050, Rio de Janeiro, Brazil 6. Laboratório de Gen?mica Funcional e Bioinformática, Instituto Oswaldo Cruz (IOC-FIOCRUZ), Funda??o Oswaldo Cruz, Av. Brasil 4365. Pavilh?o Le?nidas Deane (Pav. 26) - 1° andar- sala, 110 21040-900, Rio de Janeiro, Brazil 7. Departamento de Pediatria, Faculdade de Medicina da Universidade de S?o Paulo, Av. Dr. Enéas Carvalho de Aguiar 647, 05403-900, S?o Paulo, Brazil 8. Instituto Israelita de Ensino e Pesquisa Albert Einstein, Av. Albert Einstein 627, 05651-901, S?o Paulo, Brazil 9. Instituto de Matemática, Universidade Federal do Rio Grande do Sul, Av. Bento Gon?alves 9500 Prédio 43-111 - Agronomia, Caixa Postal 15080, Porto Alegre, Brazil 10. Núcleo Mama Moinhos, Associa??o Hospitalar Moinhos de Vento, Rua Ramiro Barcelos 910, 11°. Andar, 90035-001, Porto Alegre, Brazil 11. Servi?o 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 Gon?alves, 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 |
| 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 |
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