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. Published: 25 February 2009 Hereditary Cancer in Clinical Practice 2009, 7:5 doi:10.1186/1897-4287-7-5 Received: 8 November 2008 Accepted: 25 February 2009 This article is available from: http://www.hccpjournal.com/content/7/1/5 © 2009 Suspitsin et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

The gene products of BRCA1 and NBN (previously NBS1) play an essential role in various aspects of genomic maintenance, including regulation of DNA double-strand break repair, cell cycle control, meiosis, and telomere functioning [ [1] Eyfjord J.E. Bodvarsdottir S.K. Genomic instability and cancer: networks involved in response to DNA damage. Mutat Res. 2005; 592: 18-28 Crossref PubMed Scopus (86) Google Scholar ]. Homozygous inactivation of BRCA1 appears to confer embryonic lethality in humans, and heterozygous mutations of this gene underlie the well-known breast-ovarian hereditary cancer syndrome [ [2] Oldenburg R.A. Meijers-Heijboer H. Cornelisse C.J. Devilee P. Genetic susceptibility for breast cancer: how many more genes to be found?. Crit Rev Oncol Hematol. 2007; 63: 125-149 Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar ]. In contrast to BRCA1, biallelic germline defects of NBN are compatible with survival, although they result in the so-called Nijmegen breakage syndrome, a severe disorder consisting of developmental defects, microcephaly, mental retardation, immunodeficiency, and increased cancer risk [ [3] The International Nijmegen Breakage Syndrome Study Group Nijmegen breakage syndrome. Arch Dis Child. 2000; 82: 400-406 Crossref PubMed Scopus (265) Google Scholar ].