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Hereditary Cancer in Clinical Practice
Published in: Hereditary Cancer in Clinical Practice 1/2011

Open Access 01-12-2011 | Research

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

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

Published in: Hereditary Cancer in Clinical Practice | Issue 1/2011

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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 BRCA1 c.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 BRCA1 c.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.
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Metadata
Title
Prevalence of the BRCA1 founder mutation c.5266dupin Brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome
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
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Hereditary Cancer in Clinical Practice / Issue 1/2011
Electronic ISSN: 1897-4287
DOI
https://doi.org/10.1186/1897-4287-9-12

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