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Open Access 01-12-2011 | Research article

Genotype-phenotype correlations among BRCA14153delA and 5382insC mutation carriers from Latvia

Authors: Grigorijs Plakhins, Arvids Irmejs, Andris Gardovskis, Signe Subatniece, Santa Rozite, Marianna Bitina, Guntars Keire, Gunta Purkalne, Uldis Teibe, Genadijs Trofimovics, Edvins Miklasevics, Janis Gardovskis

Published in: BMC Medical Genetics | Issue 1/2011

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 1^st and 2^nd 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.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/12/147/prepub

Title: Genotype-phenotype correlations among BRCA14153delA and 5382insC mutation carriers from Latvia
Authors: Grigorijs Plakhins
Arvids Irmejs
Andris Gardovskis
Signe Subatniece
Santa Rozite
Marianna Bitina
Guntars Keire
Gunta Purkalne
Uldis Teibe
Genadijs Trofimovics
Edvins Miklasevics
Janis Gardovskis
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2011
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/1471-2350-12-147

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Genotype-phenotype correlations among BRCA14153delA and 5382insC mutation carriers from Latvia

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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