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Open Access Research article

Genotype-phenotype correlations among BRCA1 4153delA and 5382insC mutation carriers from Latvia

Grigorijs Plakhins12*, Arvids Irmejs13, Andris Gardovskis13, Signe Subatniece1, Santa Rozite4, Marianna Bitina5, Guntars Keire6, Gunta Purkalne2, Uldis Teibe7, Genadijs Trofimovics13, Edvins Miklasevics1 and Janis Gardovskis13

Author Affiliations

1 Hereditary Cancer Institute, Riga Stradins University, Dzirciema Street 16, Riga, LV-1007, Latvia

2 Oncology Clinic, Pauls Stradins Clinical University Hospital, Pilsonu Street 13, Riga, LV-1002, Latvia

3 Surgery Clinic, Pauls Stradins Clinical University Hospital, Pilsonu Street 13, Riga, LV-1002, Latvia

4 The Centre of Health Economics, Ministry of Health of the Republic of Latvia, Duntes Street 12/22, Riga, LV-1005, Latvia

5 Department of Oncology, Daugavpils Regional Hospital, Vasarnicu Street 20, Daugavpils, LV-5417, Latvia

6 Oncology Clinic, Liepaja Piejuras Hospital, Jurmalas Street 2, Liepaja, LV-3401, Latvia

7 Department of Physics, Riga Stradins University, Dzirciema Street 16, Riga, LV-1007, Latvia

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BMC Medical Genetics 2011, 12:147  doi:10.1186/1471-2350-12-147

Published: 27 October 2011

Abstract

Background

Mutations in the high penetrance breast and ovarian cancer susceptibility gene BRCA1 account for a significant percentage of hereditary breast and ovarian cancer cases. Genotype-phenotype correlations of BRCA1 mutations located in different parts of the BRCA1 gene have been described previously; however, phenotypic differences of specific BRCA1 mutations have not yet been fully investigated. In our study, based on the analysis of a population-based series of unselected breast and ovarian cancer cases in Latvia, we show some aspects of the genotype-phenotype correlation among the BRCA1 c.4034delA (4153delA) and c.5266dupC (5382insC) founder mutation carriers.

Methods

We investigated the prevalence of the BRCA1 founder mutations c.4034delA and c.5266dupC in a population-based series of unselected breast (n = 2546) and ovarian (n = 795) cancer cases. Among the BRCA1 mutation carriers identified in this analysis we compared the overall survival, age at diagnosis and family histories of breast and ovarian cancers.

Results

We have found that the prevalence of breast and ovarian cancer cases (breast: ovarian cancer ratio) differs significantly among the carriers of the c.5266dupC and c.4034delA founder mutations (OR = 2.98, 95%CI = 1.58 to 5.62, P < 0.001). We have also found a difference in the prevalence of breast and ovarian cancer cases among the 1st and 2nd degree relatives of the c.4034delA and c.5266dupC mutation carriers. In addition, among the breast cancer cases the c.4034delA mutation has been associated with a later age of onset and worse clinical outcomes in comparison with the c.5266dupC mutation.

Conclusions

Our data suggest that the carriers of the c.4034delA and c.5266dupC founder mutations have different risks of breast and ovarian cancer development, different age of onset and prognosis of breast cancer.