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

Prevalence of the BRCA1 founder mutation c.5266dupin Brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome - Download this document for free, or read online. Document in PDF available to download.

Hereditary Cancer in Clinical Practice

, 9:12

First Online: 20 December 2011Received: 25 April 2011Accepted: 20 December 2011


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.

KeywordsHereditary breast cancer Hereditary breast and ovarian cancer Syndrome Founder mutations BRCA1 gene BRCA2 gene AbbreviationsASCOAmerican Society of Clinical Oncology

BICBreast Cancer Information Core

BRCA1Breast Cancer 1

BRCA2Breast Cancer 2

CAPESCoordenação de Aperfeiçoamento de Pessoal de Nível Superior

CNPqConselho Nacional de Desenvolvimento Científico e Tecnológico

FIPE - HCPAFundação de Incentivo à Pesquisa do Hospital de Clínicas de Porto Alegre

FAPERGSFundação de Amparo à Pesquisa no Rio Grande do Sul

HBOCHereditary Breast and Ovarian Cancer

PCRPolymerase Chain Reaction

PRODOCPrograma de Apoio a Projetos Institucionais com a Participação de Recém - Doutores.

Download fulltext PDF

Author: Ingrid P Ewald - Patrícia Izetti - Fernando R Vargas - Miguel AM Moreira - Aline S Moreira - Carlos A Moreira-Filho -


Related documents