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Hereditary Cancer in Clinical Practice
Published in: Hereditary Cancer in Clinical Practice 1/2009

Open Access 01-12-2009 | Research

High frequency of BRCA1, but not CHEK2 or NBS1 (NBN), founder mutations in Russian ovarian cancer patients

Authors: Evgeny N Suspitsin, Nathalia Yu Sherina, Daria N Ponomariova, Anna P Sokolenko, Aglaya G Iyevleva, Tatyana V Gorodnova, Olga A Zaitseva, Olga S Yatsuk, Alexandr V Togo, Nathalia N Tkachenko, Grigory A Shiyanov, Oksana S Lobeiko, Nadezhda Yu Krylova, Dmitry E Matsko, Sergey Ya Maximov, Adel F Urmancheyeva, Nathalia V Porhanova, Evgeny N Imyanitov

Published in: Hereditary Cancer in Clinical Practice | Issue 1/2009

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Abstract

Background

A significant portion of ovarian cancer (OC) cases is caused by germ-line mutations in BRCA1 or BRCA2 genes. BRCA testing is cheap in populations with founder effect and therefore recommended for all patients with OC diagnosis. Recurrent mutations constitute the vast majority of BRCA defects in Russia, however their impact in OC morbidity has not been yet systematically studied. Furthermore, Russian population is characterized by a relatively high frequency of CHEK2 and NBS1 (NBN) heterozygotes, but it remains unclear whether these two genes contribute to the OC risk.

Methods

The study included 354 OC patients from 2 distinct, geographically remote regions (290 from North-Western Russia (St.-Petersburg) and 64 from the south of the country (Krasnodar)). DNA samples were tested by allele-specific PCR for the presence of 8 founder mutations (BRCA1 5382insC, BRCA1 4153delA, BRCA1 185delAG, BRCA1 300T>G, BRCA2 6174delT, CHEK2 1100delC, CHEK2 IVS2+1G>A, NBS1 657del5). In addition, literature data on the occurrence of BRCA1, BRCA2, CHEK2 and NBS1 mutations in non-selected ovarian cancer patients were reviewed.

Results

BRCA1 5382insC allele was detected in 28/290 (9.7%) OC cases from the North-West and 11/64 (17.2%) OC patients from the South of Russia. In addition, 4 BRCA1 185delAG, 2 BRCA1 4153delA, 1 BRCA2 6174delT, 2 CHEK2 1100delC and 1 NBS1 657del5 mutation were detected. 1 patient from Krasnodar was heterozygous for both BRCA1 5382insC and NBS1 657del5 variants.

Conclusion

Founder BRCA1 mutations, especially BRCA1 5382insC variant, are responsible for substantial share of OC morbidity in Russia, therefore DNA testing has to be considered for every OC patient of Russian origin. Taken together with literature data, this study does not support the contribution of CHEK2 in OC risk, while the role of NBS1 heterozygosity may require further clarification.
Appendix
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Metadata
Title
High frequency of BRCA1, but not CHEK2 or NBS1 (NBN), founder mutations in Russian ovarian cancer patients
Authors
Evgeny N Suspitsin
Nathalia Yu Sherina
Daria N Ponomariova
Anna P Sokolenko
Aglaya G Iyevleva
Tatyana V Gorodnova
Olga A Zaitseva
Olga S Yatsuk
Alexandr V Togo
Nathalia N Tkachenko
Grigory A Shiyanov
Oksana S Lobeiko
Nadezhda Yu Krylova
Dmitry E Matsko
Sergey Ya Maximov
Adel F Urmancheyeva
Nathalia V Porhanova
Evgeny N Imyanitov
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Hereditary Cancer in Clinical Practice / Issue 1/2009
Electronic ISSN: 1897-4287
DOI
https://doi.org/10.1186/1897-4287-7-5

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