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

Detalhes bibliográficos
Autor(a) principal: Ewald, Ingrid Petroni
Data de Publicação: 2011
Outros Autores: Ribeiro, Patrícia Lisbôa Izetti, Vargas, Fernando Regla, Moreira, Miguel Angelo Martins, Moreira, Aline S., Moreira Filho, Carlos Alberto, Cunha, Danielle Renzoni, Hamaguchi, Sara, Camey, Suzi Alves, Schmidt, Aishameriane Venes, Caleffi, Maira, Santos, Patrícia Koehler dos, Giugliani, Roberto, Prolla, Patrícia Ashton
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UFRGS
Texto Completo: http://hdl.handle.net/10183/109954
Resumo: 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.
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spelling Ewald, Ingrid PetroniRibeiro, Patrícia Lisbôa IzettiVargas, Fernando ReglaMoreira, Miguel Angelo MartinsMoreira, Aline S.Moreira Filho, Carlos AlbertoCunha, Danielle RenzoniHamaguchi, SaraCamey, Suzi AlvesSchmidt, Aishameriane VenesCaleffi, MairaSantos, Patrícia Koehler dosGiugliani, RobertoProlla, Patrícia Ashton2015-02-11T02:18:02Z20111731-2302http://hdl.handle.net/10183/109954000820915About 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.application/pdfengHereditary cancer in clinical practice. London. Vol. 9 (20 dec. 2011), [8 f.].Estatistica aplicada : MedicinaHereditary breast cancerHereditary breast and ovarian cancer SyndromeFounder mutationsBRCA1 geneBRCA2 genePrevalence of the BRCA1 founder mutation c.5266dup in brazilian individuals at-risk for the hereditary breast and ovarian cancer syndromeEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT000820915.pdf.txt000820915.pdf.txtExtracted Texttext/plain42421http://www.lume.ufrgs.br/bitstream/10183/109954/2/000820915.pdf.txt2df93799b5d61a8490200465f0586e65MD52ORIGINAL000820915.pdf000820915.pdfTexto completo (inglês)application/pdf244066http://www.lume.ufrgs.br/bitstream/10183/109954/1/000820915.pdf5eee0bdc74be42a6bee2b17c062990adMD51THUMBNAIL000820915.pdf.jpg000820915.pdf.jpgGenerated Thumbnailimage/jpeg1939http://www.lume.ufrgs.br/bitstream/10183/109954/3/000820915.pdf.jpg2f960d4a64f27e9be40714a2127e0510MD5310183/1099542023-07-12 03:34:55.385225oai:www.lume.ufrgs.br:10183/109954Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2023-07-12T06:34:55Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false
dc.title.pt_BR.fl_str_mv Prevalence of the BRCA1 founder mutation c.5266dup in brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome
title Prevalence of the BRCA1 founder mutation c.5266dup in brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome
spellingShingle Prevalence of the BRCA1 founder mutation c.5266dup in brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome
Ewald, Ingrid Petroni
Estatistica aplicada : Medicina
Hereditary breast cancer
Hereditary breast and ovarian cancer Syndrome
Founder mutations
BRCA1 gene
BRCA2 gene
title_short Prevalence of the BRCA1 founder mutation c.5266dup in brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome
title_full Prevalence of the BRCA1 founder mutation c.5266dup in brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome
title_fullStr Prevalence of the BRCA1 founder mutation c.5266dup in brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome
title_full_unstemmed Prevalence of the BRCA1 founder mutation c.5266dup in brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome
title_sort Prevalence of the BRCA1 founder mutation c.5266dup in brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome
author Ewald, Ingrid Petroni
author_facet Ewald, Ingrid Petroni
Ribeiro, Patrícia Lisbôa Izetti
Vargas, Fernando Regla
Moreira, Miguel Angelo Martins
Moreira, Aline S.
Moreira Filho, Carlos Alberto
Cunha, Danielle Renzoni
Hamaguchi, Sara
Camey, Suzi Alves
Schmidt, Aishameriane Venes
Caleffi, Maira
Santos, Patrícia Koehler dos
Giugliani, Roberto
Prolla, Patrícia Ashton
author_role author
author2 Ribeiro, Patrícia Lisbôa Izetti
Vargas, Fernando Regla
Moreira, Miguel Angelo Martins
Moreira, Aline S.
Moreira Filho, Carlos Alberto
Cunha, Danielle Renzoni
Hamaguchi, Sara
Camey, Suzi Alves
Schmidt, Aishameriane Venes
Caleffi, Maira
Santos, Patrícia Koehler dos
Giugliani, Roberto
Prolla, Patrícia Ashton
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Ewald, Ingrid Petroni
Ribeiro, Patrícia Lisbôa Izetti
Vargas, Fernando Regla
Moreira, Miguel Angelo Martins
Moreira, Aline S.
Moreira Filho, Carlos Alberto
Cunha, Danielle Renzoni
Hamaguchi, Sara
Camey, Suzi Alves
Schmidt, Aishameriane Venes
Caleffi, Maira
Santos, Patrícia Koehler dos
Giugliani, Roberto
Prolla, Patrícia Ashton
dc.subject.por.fl_str_mv Estatistica aplicada : Medicina
topic Estatistica aplicada : Medicina
Hereditary breast cancer
Hereditary breast and ovarian cancer Syndrome
Founder mutations
BRCA1 gene
BRCA2 gene
dc.subject.eng.fl_str_mv Hereditary breast cancer
Hereditary breast and ovarian cancer Syndrome
Founder mutations
BRCA1 gene
BRCA2 gene
description 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.
publishDate 2011
dc.date.issued.fl_str_mv 2011
dc.date.accessioned.fl_str_mv 2015-02-11T02:18:02Z
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dc.relation.ispartof.pt_BR.fl_str_mv Hereditary cancer in clinical practice. London. Vol. 9 (20 dec. 2011), [8 f.].
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