Research

Prevalence of the BRCA1 founder mutation c.5266dup in Brazilian individuals at-risk for the Hereditary Breast and Ovarian Cancer Syndrome

Ingrid P Ewald, Patricia R Izetti, Fernando R Vargas, Miguel A M Moreira, Aline S Moreira, Carlos A Moreira-Filho, Danielle R Cunha, Sara Hamaguchi, Suzi A Camey, Aishameriane Schmidt, Maira Caleffi, Patricia Koehler-Santos, Roberto Giugliani and Patricia Ashton-Prolla

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Hereditary Cancer in Clinical Practice 2011, 9:12 doi:10.1186/1897-4287-9-12

Published: 20 December 2011

Abstract (provisional)

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 descent, 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 (Gomes et al., 2007).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 the 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 BRCA1c.68_69del and BRCA2c.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 BRCA1c.68_69del and BRCA2c.5946del is not justified, and that screening for BRCA1c.5266dup should be considered in high risk patients, given its prevalence as a single mutation. A negative screening result should always be followed by comprehensive BRCA gene testing. The finding of a significantly higher frequency of BRCA1c.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.