High frequency of BRCA1, but not CHEK2 or NBS1 (NBN), founder mutations in Russian ovarian cancer patients
- Evgeny N Suspitsin1, 4,
- Nathalia Yu Sherina1,
- Daria N Ponomariova1,
- Anna P Sokolenko1, 4,
- Aglaya G Iyevleva1, 4,
- Tatyana V Gorodnova1,
- Olga A Zaitseva1,
- Olga S Yatsuk1,
- Alexandr V Togo1,
- Nathalia N Tkachenko6,
- Grigory A Shiyanov6,
- Oksana S Lobeiko2,
- Nadezhda Yu Krylova5,
- Dmitry E Matsko3,
- Sergey Ya Maximov2,
- Adel F Urmancheyeva2, 5,
- Nathalia V Porhanova6 and
- Evgeny N Imyanitov1, 4, 5Email author
© Suspitsin et al; licensee BioMed Central Ltd. 2009
Received: 08 November 2008
Accepted: 25 February 2009
Published: 25 February 2009
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.
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.
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.
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.
Ovarian cancer (OC) is a major cause of oncological mortality in females, with a life-time risk approaching to approximately 1.7%. Poor outcome of OC is largely attributed to the failure to diagnose the disease at early, potentially curable stages; small tumors of the ovary are usually asymptomatic and likely to be missed by routine gynecological examination . Genetic component may play a key role in OC etiology: depending on the country and ethnicity, 5–50% OC cases are attributed to the germ-line heterozygous inactivation of BRCA1 or BRCA2 genes (see additional file 1). Interestingly, while BRCA-related breast carcinomas (BC) are usually strongly enriched by early onset and familial cancer cases, this relationship is less evident for OC. Although the majority of the studies confirm some association between the presence of BRCA mutation and younger patients age (for BRCA1 but not BRCA2) or family history of the disease (see additional file 1), the strength of this trend is not enough to limit BRCA testing by particular categories of OC patients; instead, the OC diagnosis itself is often considered as a sufficient indication for BRCA analysis. Actually, the occurrence of BRCA mutations in randomly recruited OC cases is fairly similar to the estimates, which are obtained in preselected high-risk categories of women with breast cancer [2–41].
In Russia, a significant fraction of early-onset and/or bilateral and/or familial BC cases is caused by founder mutations in cancer genes . Presence of the "founder effect" significantly decreases the costs of the DNA testing, thus relaxing the criteria for patients selection. While distribution of germ-line mutations in Russian breast cancer cases has been studied with sufficient level of comprehension, no systematic analysis has been undertaken yet for ovarian cancer. Furthermore, breast cancer in Russia and some neighboring countries is caused not only by mutations in BRCA genes, but also by heterozygous inactivation of the CHEK2 and NBS1 . It remains unclear, whether the latter 2 genes contribute to OC predisposition as well, or, vice versa, their impact is limited by breast cancer risk.
Materials and methods
Ovarian cancer cases were collected in 2 geographically distinct regions of Russian Federation. 290 patients (mean age: 53 years; age range: 21–89 years) were recruited in the N.N. Petrov Institute of Oncology (St.-Petersburg), which provides the treatment to the residents of North-Western Russia. In addition, the study included 64 women with OC (mean age: 59 years; age range: 33–78 years) from the regional oncological hospital of the city of Krasnodar, which is located in Southern Russia, more than two thousands kilometers aside from the first spot of patients collection. Almost all patients had Slavic ethnic origin. DNA isolation, design of PCR assays and other relevant technical information is described in detail in our earlier report .
Founder mutations in Russian ovarian cancer cases
St.-Petersburg (n = 290)
Krasnodar (n = 64)
Frequencies of founder mutations in distinct categories of ovarian cancer patients
St.-Petersburg (n = 290)
Krasnodar (n = 64)
Age at onset (years)
Adenocarcinoma, not otherwise specified
This study was designed to analyze the impact of selected founder mutations in OC morbidity in Russia. The panel of genetic variants included several alleles, which are characteristic for Slavic people and/or residents of Baltic regions (BRCA1 5382insC, BRCA1 4153delA, BRCA1 300T>G, CHEK2 1100delC, CHEK2 IVS2+1G>A, NBS1 657del5), and/or European Jews (BRCA1 185delAG, BRCA2 6174delT). This study confirmed the utmost role of BRCA1 5382insC mutation in cancer morbidity: indeed, this single genetic defect is responsible for as many as 1 out of 9 ovarian cancers and 1 out of 25 breast cancers occurring in Russia. Furthermore, BRCA1 5382insC demonstrates unique geographic spread, being among the most prevalent BRCA variants in Poland, Byelorussia, Baltic republics, various cities of Russian Federation (St.-Petersburg, Tomsk, and Krasnodar), and possibly some Mediterranean countries [42, 44–49]. The remarkable role of the founder effect contradicts to the wide-spread view that the extreme complexity of the history of Russian Empire resulted in huge genetic diversity of Russian residents. It is important to emphasize, that recent investigations show surprisingly high level of genetic homogeneity for the 3 analyzed Slavic-speaking populations, i.e. Russians, Ukrainians and Poles . These unexpected data are in good agreement with the lack of language diversity within the Russian Federation: astonishingly, people residing nearby Baltic sea or in the Far East speak exactly the same dialect, despite being separated by the distance of 11000 kilometers.
Other BRCA1 founder mutations are relatively rare in Russian ovarian or breast cancer cases . BRCA1 4153delA allele was initially considered to be characteristic for familial OC in Russia ; furthermore, it was suggested that this variant confers specific predisposition to the ovarian but not breast carcinogenesis [25, 48]. Our data do not confirm these statements. Jewish BRCA1 185delAG allele is occasionally detected in Russian OC and BC cases, while Baltic BRCA1 300T>G variant demonstrates null occurrence and therefore has to be excluded from the local diagnostic panel . Taken together with other reports on OC patients or healthy controls [36–38, 51], this study does not support the role of CHEK2 gene lesions in OC predisposition (Table 1). On the other hand, the possibility of limited contribution of NBS1 germ-line mutations in OC risk cannot be fully excluded. Previously, Plisiecka-Hałasa et al.  identified 2 NBS1 657del5 mutation carriers among 117 OC patients. In the present study, the frequency of NBS1 heterozygosity in OC patients (0.3%) did not differ significantly from the estimate obtained in healthy Russian women (0.6%) . However, tumor tissue from the BRCA1/NBS1 heterozygous carrier from our OC group contained biallelic inactivation of NBS1 but not BRCA1 .
Most of the published investigations reported a correlation between the presence of BRCA1 mutation and family history of breast/ovarian cancer as well as earlier onset of the disease. Some reports also noticed association of BRCA1 heterozygosity with non-mucinous tumor histology, high tumor grade, and improved survival (see additional file 1). Nevertheless, almost all investigators agree that neither lack of family history nor late disease onset are reliable indicators of BRCA1 wild-type status in OC patients, therefore DNA testing of non-selected ovarian cancer cases is recommended by some laboratories. Our study failed to detect relationships between BRCA1 germ-line mutations and first-degree family history. There are some factors, which could complicate the analysis of pedigrees for BC and OC cases. First of all, BRCA1-related cancers are mainly gender-specific: i.e. male carriers of BRCA1 defects do not experience significantly elevated cancer risk due to absence of the main target organs (breasts and ovaries); therefore, family history negative BRCA1-associated BC and OC are particularly likely in case of paternal transmission of the mutation. Other confounding effects are related to specific circumstances of recent history of Russian Federation. Huge human losses caused by historical turbulences in the XX century, taken together with limited average life expectancy, led to the situation when many BRCA1 carriers simply failed to achieve the age of cancer manifestation due to premature death. Another factor, that may increase the number of false-negative pedigrees, is a relatively low number of children per family in the modern Russia; in other words, many of questioned patients could recall only a small number if any of their adult female relatives. Finally, an analysis of heredity is frequently ignored by Russian medical professionals, i.e. family history records in medical charts may simply lack a sufficient level of accuracy.
This study indicates that all ovarian cancer patients of Russian ethnic origin have to be screened for the presence of a few BRCA1 founder mutations (BRCA1 5382insC, BRCA1 185delAG, BRCA1 4153delA). Introduction of this cheap DNA test into routine medical practice may help to identify yet healthy relatives of OC patients, who carry the same genetic defect and thus will benefit from tight surveillance and/or prophylactic surgery. Furthermore, recent findings suggest that BRCA1-associated ovarian cancers may require distinct strategy for the disease treatment .
This work is supported by INTAS (grant 05-1000008-7870), Grant for Helmholtz-Russia Joint Research Groups (grant HRJRG-006/07-04-92282-à), Russian Foundation for Basic Research (grants 07-04-00122-à, 07-04-00172-à, 08-04-00369-à), and the Russian Academy of Sciences (grant "Molecular and Cell Biology"). We cordially thank Prof. Peter Devilee (Leiden University Medical Center, The Netherlands) for the fruitful discussion.
- DeVita VT Jr, Hellman S, Rosenberg SA, Eds: Cancer principles and practice in oncology. eighth edition. Lippincott Williams and Wilkins; 2008.Google Scholar
- Abeliovich D, Kaduri L, Lerer I, Weinberg N, Amir G, Sagi M, Zlotogora J, Heching N, Peretz T: The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women. Am J Hum Genet 1997, 60: 505–514.PubMedPubMed CentralGoogle Scholar
- Beller U, Halle D, Catane R, Kaufman B, Hornreich G, Levy-Lahad E: High frequency of BRCA1 and BRCA2 germline mutations in Ashkenazi Jewish ovarian cancer patients, regardless of family history. Gynecol Oncol 1997, 67: 123–126. 10.1006/gyno.1997.4844View ArticlePubMedGoogle Scholar
- Ramus SJ, Fishman A, Pharoah PD, Yarkoni S, Altaras M, Ponder BA: Ovarian cancer survival in Ashkenazi Jewish patients with BRCA1 and BRCA2 mutations. Eur J Surg Oncol 2001, 27: 278–281. 10.1053/ejso.2000.1097View ArticlePubMedGoogle Scholar
- Cass I, Baldwin RL, Varkey T, Moslehi R, Narod SA, Karlan BY: Improved survival in women with BRCA-associated ovarian carcinoma. Cancer 2003, 97: 2187–2195. 10.1002/cncr.11310View ArticlePubMedGoogle Scholar
- Tobias DH, Eng C, McCurdy LD, Kalir T, Mandelli J, Dottino PR, Cohen CJ: Founder BRCA 1 and 2 mutations among a consecutive series of Ashkenazi Jewish ovarian cancer patients. Gynecol Oncol 2000, 78: 148–151. 10.1006/gyno.2000.5848View ArticlePubMedGoogle Scholar
- Boyd J, Sonoda Y, Federici MG, Bogomolniy F, Rhei E, Maresco DL, Saigo PE, Almadrones LA, Barakat RR, Brown CL, Chi DS, Curtin JP, Poynor EA, Hoskins WJ: Clinicopathologic features of BRCA-linked and sporadic ovarian cancer. JAMA 2000, 283: 2260–2265. 10.1001/jama.283.17.2260View ArticlePubMedGoogle Scholar
- Satagopan JM, Boyd J, Kauff ND, Robson M, Scheuer L, Narod S, Offit K: Ovarian cancer risk in Ashkenazi Jewish carriers of BRCA1 and BRCA2 mutations. Clin Cancer Res 2002, 8: 3776–3781.PubMedGoogle Scholar
- Moslehi R, Chu W, Karlan B, Fishman D, Risch H, Fields A, Smotkin D, Ben-David Y, Rosenblatt J, Russo D, Schwartz P, Tung N, Warner E, Rosen B, Friedman J, Brunet JS, Narod SA: BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer. Am J Hum Genet 2000, 66: 1259–1272. 10.1086/302853View ArticlePubMedPubMed CentralGoogle Scholar
- Tong D, Stimpfl M, Reinthaller A, Vavra N, Müllauer-Ertl S, Leodolter S, Zeillinger R: BRCA1 gene mutations in sporadic ovarian carcinomas: detection by PCR and reverse allele-specific oligonucleotide hybridization. Clin Chem 1999, 45: 976–981.PubMedGoogle Scholar
- Tonin PN, Mes-Masson AM, Narod SA, Ghadirian P, Provencher D: Founder BRCA1 and BRCA2 mutations in French Canadian ovarian cancer cases unselected for family history. Clin Genet 1999, 55: 318–324. 10.1034/j.1399-0004.1999.550504.xView ArticlePubMedGoogle Scholar
- Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Kwan E, Jack E, Vesprini DJ, Kuperstein G, Abrahamson JL, Fan I, Wong B, Narod SA: Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet 2001, 68: 700–710. 10.1086/318787View ArticlePubMedPubMed CentralGoogle Scholar
- Zikan M, Pohlreich P, Stribrna J: Mutational analysis of the BRCA1 gene in 30 Czech ovarian cancer patients. J Genet 2005, 84: 63–67. 10.1007/BF02715891View ArticlePubMedGoogle Scholar
- Sarantaus L, Vahteristo P, Bloom E, Tamminen A, Unkila-Kallio L, Butzow R, Nevanlinna H: BRCA1 and BRCA2 mutations among 233 unselected Finnish ovarian carcinoma patients. Eur J Hum Genet 2001, 9: 424–430. 10.1038/sj.ejhg.5200652View ArticlePubMedGoogle Scholar
- Looij M, Szabo C, Besznyak I, Liszka G, Csokay B, Pulay T, Toth J, Devilee P, King MC, Olah E: Prevalence of founder BRCA1 and BRCA2 mutations among breast and ovarian cancer patients in Hungary. Int J Cancer 2000, 86: 737–740. 10.1002/(SICI)1097-0215(20000601)86:5<737::AID-IJC21>3.0.CO;2-1View ArticleGoogle Scholar
- Johannesdottir G, Gudmundsson J, Bergthorsson JT, Arason A, Agnarsson BA, Eiriksdottir G, Johannsson OT, Borg A, Ingvarsson S, Easton DF, Egilsson V, Barkardottir RB: High prevalence of the 999del5 mutation in icelandic breast and ovarian cancer patients. Cancer Res 1996, 56: 3663–3665.PubMedGoogle Scholar
- Hirsh-Yechezkel G, Chetrit A, Lubin F, Friedman E, Peretz T, Gershoni R, Rizel S, Struewing JP, Modan B: Population attributes affecting the prevalence of BRCA mutation carriers in epithelial ovarian cancer cases in Israel. Gynecol Oncol 2003, 89: 494–498. 10.1016/S0090-8258(03)00152-5View ArticlePubMedGoogle Scholar
- Ben David Y, Chetrit A, Hirsh-Yechezkel G, Friedman E, Beck BD, Beller U, Ben-Baruch G, Fishman A, Levavi H, Lubin F, Menczer J, Piura B, Struewing JP, Modan B, National Israeli Study of Ovarian Cancer: Effect of BRCA mutations on the length of survival in epithelial ovarian tumors. J Clin Oncol 2002, 20: 463–466. 10.1200/JCO.20.2.463View ArticlePubMedGoogle Scholar
- Chetrit A, Hirsh-Yechezkel G, Ben-David Y, Lubin F, Friedman E, Sadetzki S: Effect of BRCA1/2 mutations on long-term survival of patients with invasive ovarian cancer: the national Israeli study of ovarian cancer. J Clin Oncol 2008, 26: 20–25. 10.1200/JCO.2007.11.6905View ArticlePubMedGoogle Scholar
- Matsushima M, Kobayashi K, Emi M, Saito H, Saito J, Suzumori K, Nakamura Y: Mutation analysis of the BRCA1 gene in 76 Japanese ovarian cancer patients: four germline mutations, but no evidence of somatic mutation. Hum Mol Genet 1995, 4: 1953–1956. 10.1093/hmg/4.10.1953View ArticlePubMedGoogle Scholar
- Kim YT, Nam EJ, Yoon BS, Kim SW, Kim SH, Kim JH, Kim HK, Koo JS, Kim JW: Germline mutations of BRCA1 and BRCA2 in Korean sporadic ovarian carcinoma. Gynecol Oncol 2005, 99: 585–590. 10.1016/j.ygyno.2005.06.058View ArticlePubMedGoogle Scholar
- Dørum A, Hovig E, Tropé C, Inganas M, Møller P: Three per cent of Norwegian ovarian cancers are caused by BRCA1 1675delA or 1135insA. Eur J Cancer 1999, 35: 779–781. 10.1016/S0959-8049(99)00050-7View ArticlePubMedGoogle Scholar
- Jacobi CE, van Ierland Y, van Asperen CJ, Hallensleben E, Devilee P, Jan Fleuren G, Kenter GG: Prediction of BRCA1/2 mutation status in patients with ovarian cancer from a hospital-based cohort. Genet Med 2007, 9: 173–179.View ArticlePubMedGoogle Scholar
- Liede A, Malik IA, Aziz Z, Rios Pd Pde L, Kwan E, Narod SA: Contribution of BRCA1 and BRCA2 mutations to breast and ovarian cancer in Pakistan. Am J Hum Genet 2002, 71: 595–606. 10.1086/342506View ArticlePubMedPubMed CentralGoogle Scholar
- Menkiszak J, Gronwald J, Górski B, Jakubowska A, Huzarski T, Byrski T, Foszczyńska-Kłoda M, Haus O, Janiszewska H, Perkowska M, Brozek I, Grzybowska E, Zientek H, Góźdź S, Kozak-Klonowska B, Urbański K, Miturski R, Kowalczyk J, Pluzańska A, Niepsuj S, Koc J, Szwiec M, Drosik K, Mackiewicz A, Lamperska K, Strózyk E, Godlewski D, Stawicka M, Waśko B, Bebenek M, Rozmiarek A, Rzepka-Górska I, Narod SA, Lubiński J: Hereditary ovarian cancer in Poland. Int J Cancer 2003, 106: 942–945. 10.1002/ijc.11338View ArticlePubMedGoogle Scholar
- Brozek I, Ochman K, Debniak J, Morzuch L, Ratajska M, Stepnowska M, Stukan M, Emerich J, Limon J: High frequency of BRCA1/2 germline mutations in consecutive ovarian cancer patients in Poland. Gynecol Oncol 2008, 108: 433–437. 10.1016/j.ygyno.2007.09.035View ArticlePubMedGoogle Scholar
- Malander S, Ridderheim M, Måsbäck A, Loman N, Kristoffersson U, Olsson H, Nilbert M, Borg A: One in 10 ovarian cancer patients carry germ line BRCA1 or BRCA2 mutations: results of a prospective study in Southern Sweden. Eur J Cancer 2004, 40: 422–428. 10.1016/j.ejca.2003.09.016View ArticlePubMedGoogle Scholar
- Yazici H, Glendon G, Yazici H, Burnie SJ, Saip P, Buyru F, Bengisu E, Andrulis IL, Dalay N, Ozcelik H: BRCA1 and BRCA2 mutations in Turkish familial and non-familial ovarian cancer patients: a high incidence of mutations in non-familial cases. Hum Mutat 2002, 20: 28–34. 10.1002/humu.10090View ArticlePubMedGoogle Scholar
- Stratton JF, Gayther SA, Russell P, Dearden J, Gore M, Blake P, Easton D, Ponder BA: Contribution of BRCA1 mutations to ovarian cancer. N Engl J Med 1997, 336: 1125–1130. 10.1056/NEJM199704173361602View ArticlePubMedGoogle Scholar
- Takahashi H, Chiu HC, Bandera CA, Behbakht K, Liu PC, Couch FJ, Weber BL, LiVolsi VA, Furusato M, Rebane BA, Cardonick A, Benjamin I, Morgan MA, King SA, Mikuta JJ, Rubin SC, Boyd J: Mutations of the BRCA2 gene in ovarian carcinomas. Cancer Res 1996, 56: 2738–2741.PubMedGoogle Scholar
- Takahashi H, Behbakht K, McGovern PE, Chiu HC, Couch FJ, Weber BL, Friedman LS, King MC, Furusato M, LiVolsi VA, Menzin AW, Liu PC, Benjamin I, Morgan MA, King SA, Rebane BA, Cardonick A, Mikuta JJ, Rubin SC, Boyd J: Mutation analysis of the BRCA1 gene in ovarian cancers. Cancer Res 1995, 55: 2998–3002.PubMedGoogle Scholar
- Rubin SC, Blackwood MA, Bandera C, Behbakht K, Benjamin I, Rebbeck TR, Boyd J: BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in an unselected ovarian cancer population: relationship to family history and implications for genetic testing. Am J Obstet Gynecol 1998, 178: 670–677. 10.1016/S0002-9378(98)70476-4View ArticlePubMedGoogle Scholar
- Anton-Culver H, Cohen PF, Gildea ME, Ziogas A: Characteristics of BRCA1 mutations in a population-based case series of breast and ovarian cancer. Eur J Cancer 2000, 36: 1200–1208. 10.1016/S0959-8049(00)00110-6View ArticlePubMedGoogle Scholar
- Smith SA, Richards WE, Caito K, Hanjani P, Markman M, DeGeest K, Gallion HH: BRCA1 germline mutations and polymorphisms in a clinic-based series of ovarian cancer cases: a Gynecologic Oncology Group study. Gynecol Oncol 2001, 83: 586–592. 10.1006/gyno.2001.6430View ArticlePubMedGoogle Scholar
- Pal T, Permuth-Wey J, Betts JA, Krischer JP, Fiorica J, Arango H, LaPolla J, Hoffman M, Martino MA, Wakeley K, Wilbanks G, Nicosia S, Cantor A, Sutphen R: BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer 2005, 104: 2807–2816. 10.1002/cncr.21536View ArticlePubMedGoogle Scholar
- Szymanska-Pasternak J, Szymanska A, Medrek K, Imyanitov EN, Cybulski C, Gorski B, Magnowski P, Dziuba I, Gugala K, Debniak B, Gozdz S, Sokolenko AP, Krylova NY, Lobeiko OS, Narod SA, Lubinski J: CHEK2 variants predispose to benign, borderline and low-grade invasive ovarian tumors. Gynecol Oncol 2006, 102: 429–431. 10.1016/j.ygyno.2006.05.040View ArticlePubMedGoogle Scholar
- Baysal BE, DeLoia JA, Willett-Brozick JE, Goodman MT, Brady MF, Modugno F, Lynch HT, Conley YP, Watson P, Gallion HH: Analysis of CHEK2 gene for ovarian cancer susceptibility. Gynecol Oncol 2004, 95: 62–69. 10.1016/j.ygyno.2004.07.015View ArticlePubMedGoogle Scholar
- Williams LH, Choong D, Johnson SA, Campbell IG: Genetic and epigenetic analysis of CHEK2 in sporadic breast, colon, and ovarian cancers. Clin Cancer Res 2006, 12: 6967–6972. 10.1158/1078-0432.CCR-06-1770View ArticlePubMedGoogle Scholar
- Plisiecka-Hałasa J, Dansonka-Mieszkowska A, Rembiszewska A, Bidziński M, Steffen J, Kupryjańczyk J: Nijmegen breakage syndrome gene (NBS1) alterations and its protein (nibrin) expression in human ovarian tumours. Ann Hum Genet 2002, 66: 353–359.View ArticlePubMedGoogle Scholar
- Steffen J, Varon R, Mosor M, Maneva G, Maurer M, Stumm M, Nowakowska D, Rubach M, Kosakowska E, Ruka W, Nowecki Z, Rutkowski P, Demkow T, Sadowska M, Bidziński M, Gawrychowski K, Sperling K: Increased cancer risk of heterozygotes with NBS1 germline mutations in Poland. Int J Cancer 2004, 111: 67–71. 10.1002/ijc.20239View ArticlePubMedGoogle Scholar
- Fackenthal JD, Olopade OI: Breast cancer risk associated with BRCA1 and BRCA2 in diverse populations. Nat Rev Cancer 2007, 7: 937–948. 10.1038/nrc2054View ArticlePubMedGoogle Scholar
- Sokolenko AP, Rozanov ME, Mitiushkina NV, Sherina NY, Iyevleva AG, Chekmariova EV, Buslov KG, Shilov ES, Togo AV, Bit-Sava EM, Voskresenskiy DA, Chagunava OL, Devilee P, Cornelisse C, Semiglazov VF, Imyanitov EN: Founder mutations in early-onset, familial and bilateral breast cancer patients from Russia. Fam Cancer 2007, 6: 281–286. 10.1007/s10689-007-9120-5View ArticlePubMedGoogle Scholar
- Porhanova NV, Sokolenko AP, Sherina NYu, Ponomariova DN, Tkachenko NN, Matsko DE, Imyanitov EN: Ovarian cancer patient with germ-line mutation in both BRCA1 and NBS1 (NBN) genes. Cancer Genet Cytogenet 2008, 186: 122–124. 10.1016/j.cancergencyto.2008.06.012View ArticlePubMedGoogle Scholar
- Gayther SA, Harrington P, Russell P, Kharkevich G, Garkavtseva RF, Ponder BA: Frequently occurring germ-line mutations of the BRCA1 gene in ovarian cancer families from Russia. Am J Hum Genet 1997, 60: 1239–1242.PubMedPubMed CentralGoogle Scholar
- Oszurek O, Gorski B, Gronwald J, Prosolow Z, Uglanica K, Murinow A, Bobko I, Downar O, Zlobicz M, Norik D, Byrski T, Jakubowska A, Lubinski J: Founder mutations in the BRCA1 gene in west Belarusian breast-ovarian cancer families. Clin Genet 2001, 60: 470–471. 10.1034/j.1399-0004.2001.600611.xView ArticlePubMedGoogle Scholar
- Ladopoulou A, Kroupis C, Konstantopoulou I, Ioannidou-Mouzaka L, Schofield AC, Pantazidis A, Armaou S, Tsiagas I, Lianidou E, Efstathiou E, Tsionou C, Panopoulos C, Mihalatos M, Nasioulas G, Skarlos D, Haites NE, Fountzilas G, Pandis N, Yannoukakos D: Germ line BRCA1 & BRCA2 mutations in Greek breast/ovarian cancer families: 5382insC is the most frequent mutation observed. Cancer Lett 2002, 185: 61–70. 10.1016/S0304-3835(01)00845-XView ArticlePubMedGoogle Scholar
- Tereschenko IV, Basham VM, Ponder BA, Pharoah PD: BRCA1 and BRCA2 mutations in Russian familial breast cancer. Hum Mutat 2002, 19: 184. 10.1002/humu.9008View ArticlePubMedGoogle Scholar
- Górski B, Cybulski C, Huzarski T, Byrski T, Gronwald J, Jakubowska A, Stawicka M, Gozdecka-Grodecka S, Szwiec M, Urbański K, Mituś J, Marczyk E, Dziuba J, Wandzel P, Surdyka D, Haus O, Janiszewska H, Debniak T, Tołoczko-Grabarek A, Medrek K, Masojæ B, Mierzejewski M, Kowalska E, Narod SA, Lubiński J: Breast cancer predisposing alleles in Poland. Breast Cancer Res Treat 2005, 92: 19–24. 10.1007/s10549-005-1409-1View ArticlePubMedGoogle Scholar
- Tikhomirova L, Sinicka O, Smite D, Eglitis J, Hodgson SV, Stengrevics A: High prevalence of two BRCA1 mutations, 4154delA and 5382insC, in Latvia. Fam Cancer 2005, 4: 77–84. 10.1007/s10689-004-2758-3View ArticlePubMedGoogle Scholar
- Balanovsky O, Rootsi S, Pshenichnov A, Kivisild T, Churnosov M, Evseeva I, Pocheshkhova E, Boldyreva M, Yankovsky N, Balanovska E, Villems R: Two sources of the Russian patrilineal heritage in their Eurasian context. Am J Hum Genet 2008, 82: 236–250. 10.1016/j.ajhg.2007.09.019View ArticlePubMedPubMed CentralGoogle Scholar
- Chekmariova EV, Sokolenko AP, Buslov KG, Iyevleva AG, Ulibina YM, Rozanov ME, Mitiushkina NV, Togo AV, Matsko DE, Voskresenskiy DA, Chagunava OL, Devilee P, Cornelisse C, Semiglazov VF, Imyanitov EN: CHEK2 1100delC mutation is frequent among Russian breast cancer patients. Breast Cancer Res Treat 2006, 100: 99–102. 10.1007/s10549-006-9227-7View ArticlePubMedGoogle Scholar
- Buslov KG, Iyevleva AG, Chekmariova EV, Suspitsin EN, Togo AV, Kuligina ESh, Sokolenko AP, Matsko DE, Turkevich EA, Lazareva YR, Chagunava OL, Bit-Sava EM, Semiglazov VF, Devilee P, Cornelisse C, Hanson KP, Imyanitov EN: NBS1 657del5 mutation may contribute only to a limited fraction of breast cancer cases in Russia. Int J Cancer 2005, 114: 585–589. 10.1002/ijc.20765View ArticlePubMedGoogle Scholar
- Kauff ND: Is it time to stratify for BRCA mutation status in therapeutic trials in ovarian cancer? J Clin Oncol 2008, 26: 9–10. 10.1200/JCO.2007.14.0244View ArticlePubMedGoogle Scholar
This article is published under license to 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.