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BRCA1 mutations in women with familial or early-onset breast cancer and BRCA2 mutations in familial cancer in Estonia

Kristiina Tamboom12*, Krista Kaasik37, Jelena Aršavskaja1, Mare Tekkel1, Aili Lilleorg12, Peeter Padrik6, Andres Metspalu345 and Toomas Veidebaum1

Author Affiliations

1 National Institute for Health Development, Tallinn, Estonia

2 North Estonia Medical Centre, Diagnostics Division, Tallinn, Estonia

3 Institute of Molecular and Cell Biology of the University of Tartu, Tartu, Estonia

4 Estonian Biocentre, Tartu, Estonia

5 The Estonian Genome Center of the University of Tartu, Tartu, Estonia

6 Clinic of the Hematology and Oncology, Tartu University Hospital, Tartu, Estonia

7 Department of Neurology, UCSF, CA 94158-2324, USA

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Hereditary Cancer in Clinical Practice 2010, 8:4  doi:10.1186/1897-4287-8-4

Published: 9 April 2010



The aim of this study was to identify BRCA1 and BRCA2 mutations in the Estonian population. We analyzed genetic data and questionnaire from 64 early-onset (< 45 y) breast cancer patients, 47 familial cases (patients with breast or ovarian cancer and a case of these cancers in the family), and 33 predictive cases (patients without breast or ovarian cancer, with a family history of such diseases) from Estonia for mutations in the BRCA1 gene. A sub-set of familial cases and predictive cases were also analyzed for mutations in the BRCA2 gene.


For mutation detection, we used the Polymerase Chain Reaction-Single Stranded Conformation Polymorphism Heteroduplex Analysis (PCR-SSCP-HD), followed by direct DNA sequencing.


We identified three clinically important mutations in the BRCA1 gene, including seven occurrences of the c.5382insC mutation, three of c.4154delA, and one instance of c.3881_3882delGA. We also detected six polymorphisms: c.2430T>C, c.3232A>G, c.4158A>G, c.4427T>C, c.4956A>G, and c.5002T>C. Four sequence alterations were detected in introns: c.560+64delT, c.560+ [36-38delCTT, 52-63del12], c.666-58delT, and c.5396+60insGTATTCCACTCC. In the BRCA2 gene, two clinically important mutations were found: c.9610C>T and c.6631delTTAAATG. Additionally, two alterations (c.7049G>T and c.7069+80delTTAG) with unknown clinical significance were detected.


In our dataset, the overall frequency of clinically important BRCA1 mutations in early-onset patients, familial cases, and predictive testing was 7.6% (144 cases, 11 mutation carriers). Pathogenic mutations were identified in 4 of the 64 early-onset breast cancer cases (6.3%). In familial cases, clinically important mutations in the BRCA1 gene were found in 6 of the 47 individuals analyzed (12.8%). In predictive cases, 1 clinically important mutation was detected in 33 individuals studied (3%). The occurrence of clinically important mutations in BRCA2 in familial cases of breast cancer was 2 of the 16 individuals analyzed (12.5%).