Prevalence of the BRCA1 founder mutation c.5266dup in brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome
Autor(a) principal: | |
---|---|
Data de Publicação: | 2011 |
Outros Autores: | , , , , , , , , , , , , |
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. |
id |
UFRGS-2_d0b91d10b7a4f72c43b35913b8475140 |
---|---|
oai_identifier_str |
oai:www.lume.ufrgs.br:10183/109954 |
network_acronym_str |
UFRGS-2 |
network_name_str |
Repositório Institucional da UFRGS |
repository_id_str |
|
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 |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/109954 |
dc.identifier.issn.pt_BR.fl_str_mv |
1731-2302 |
dc.identifier.nrb.pt_BR.fl_str_mv |
000820915 |
identifier_str_mv |
1731-2302 000820915 |
url |
http://hdl.handle.net/10183/109954 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Hereditary cancer in clinical practice. London. Vol. 9 (20 dec. 2011), [8 f.]. |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFRGS instname:Universidade Federal do Rio Grande do Sul (UFRGS) instacron:UFRGS |
instname_str |
Universidade Federal do Rio Grande do Sul (UFRGS) |
instacron_str |
UFRGS |
institution |
UFRGS |
reponame_str |
Repositório Institucional da UFRGS |
collection |
Repositório Institucional da UFRGS |
bitstream.url.fl_str_mv |
http://www.lume.ufrgs.br/bitstream/10183/109954/2/000820915.pdf.txt http://www.lume.ufrgs.br/bitstream/10183/109954/1/000820915.pdf http://www.lume.ufrgs.br/bitstream/10183/109954/3/000820915.pdf.jpg |
bitstream.checksum.fl_str_mv |
2df93799b5d61a8490200465f0586e65 5eee0bdc74be42a6bee2b17c062990ad 2f960d4a64f27e9be40714a2127e0510 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS) |
repository.mail.fl_str_mv |
|
_version_ |
1815447576507318272 |