Summary
Mutant alleles of several genes in the DNA repair pathway have been found to predispose women to breast cancer. From a public health perspective, the importance of a given allele in a population is determined by the frequency of the allele and by the relative risk of breast cancer that it confers. In Poland founder alleles of the BRCA1, CHEK2 and NBS1 genes have been associated with an increased risk of breast cancer, but the relative contribution of each of these alleles to the overall breast cancer burden has not yet been determined. We screened 2012 unselected cases of breast cancer and 4000 population controls for 7 different mutations in these genes. Overall, a mutation was found in 12% of the cases and in 6% of the controls. Mutations in BRCA1 and CHEK2 contributed in approximately equal measure to the burden of breast cancer in Poland. A BRCA1 mutation was present in 3% of the cases. The missense BRCA1 mutation C61G was associated with a higher odds ratio for breast cancer (OR=15) than were either of the truncating BRCA1 mutations 4153delA (OR=2.0) and 5382insC (OR=6.2). In contrast, a higher odds ratio was seen for truncating CHEK2 mutations (OR=2.1) than for the missense mutation I157T (OR=1.4). This study suggests that cancer risks may be specific for particular alleles of a susceptibility gene and that these different risks should be taken into account by genetic counselors.
Similar content being viewed by others
References
B Górski T Byrski T Huzarski A Jakubowska J Menkiszak J Gronwald A Pluzanska M Bebenek L Fischer-Maliszewska E Grzybowska SA Narod J Lubiński (2000) ArticleTitleFounder mutations in the BRCA1 gene in Polish families with breast–ovarian cancer Am J Hum Genet 66 1963–1968 Occurrence Handle10.1086/302922 Occurrence Handle1:CAS:528:DC%2BD3cXntV2ju7w%3D Occurrence Handle10788334
B Górski A Jakubowska T Huzarski T Byrski J Gronwald E Grzybowska A Mackiewicz M Stawicka M Bębenek D Sorokin Ł Fiszer-Maliszewska O Haus H Janiszewska S Niepsuj S Góźdź L Zaremba M Posmyk M Płużańska E Kilar D Czudowska B Waśko R Miturski JR Kowalczyk K Urbański M Szwiec J Koc A Rozmiarek T Dębniak C Cybulski E Kowalska A Tołoczko-Grabarek S Zajączek J Menkiszak K Mędrek B Masojć M Mierzejewski S Narod J Lubiński (2004) ArticleTitleA high proportion of founder BRCA1 mutations in Polish breast cancer families Int J Cancer 110 683–686 Occurrence Handle10.1002/ijc.20162 Occurrence Handle15146557
G Johannesdottir J Gudmundsson JT Bergthorsson A Arason BA Agnarsson G Eiriksdottir OT Johannsson A, Borg S Ingvarsson DF Easton V Egilsson RB Barkardottir (1996) ArticleTitleHigh prevalence of the 999del5 mutation in Icelandic breast and ovarian cancer patients Cancer Res 56 3663–3665 Occurrence Handle1:CAS:528:DyaK28XltVKksro%3D Occurrence Handle8706004
JP Struewing RE Tarone LC Brody FP Li JD Boice SuffixJr. (1996) ArticleTitleBRCA1 mutations in young women with breast cancer Lancet 347(9013) 1493 Occurrence Handle10.1016/S0140-6736(96)91732-8
The CHEK2 Breast Cancer Consortium: Low-penetrance susceptibility to breast cancer due to CHEK2*1100delC genetic variant contributing to a substantial fraction of familial breast cancer. Nat Genet 31: 55–59, 2002
B Gorski T Dębniak B Masojc M Mierzejewski M Medrek K Medrek C Cybulski A Jakubowska G Kurzawski M Chosia R Scott J Lubinski (2003) ArticleTitleGermline 657del5 mutation in the NBS1 gene in breast cancer patients Int J Cancer 106 379–381 Occurrence Handle10.1002/ijc.11231 Occurrence Handle1:CAS:528:DC%2BD3sXlvF2hsr4%3D Occurrence Handle12845677
K Offit H Pierce T Kirchhoff P Kolachana B Rapaport P Gregerson S Johnson O Yossepowitch H Huang J Satagopan M Robson L Scheuer K Nafa N Ellis (2003) ArticleTitleFrequency of CHEK2*1100 delC in New York breast cancer cases and controls BMC Med Genet 4 1 Occurrence Handle10.1186/1471-2350-4-1 Occurrence Handle12529183
C Cybulski T Huzarski B Górski B Masojć M Mierzejewski T Dębniak B Gliniewicz J Matyjasik E Złowocka G Kurzawski A Sikorski M Posmyk M Szwiec R Czajka SA Narod J Lubiński (2004) ArticleTitleA novel founder CHEK2 mutation is associated with increased prostate cancer risk Cancer Res 64 2677–2679 Occurrence Handle1:CAS:528:DC%2BD2cXjtV2lt7w%3D Occurrence Handle15087378
Masojć B, Mierzejewski M, Gorski B: Constitutional Mutations in NBS1 Gene in Patients with Sporadic and Hereditary Cancer of Mammary Gland, Book of Abstracts. International Congress for Students and Young Physicans, Warsaw, Poland, 2001
Steffen J, Varon R, Thomas M, Stumm M, Maurer M, Nowakowska D, et al.: The Frequency of Heterozygous Germline Mutation 657del5 in Cancer Patients from Poland. Cs.Lek.Csk. 141,202 C suppl. 8, Book of Abstracts. International Workshop on Nijmegen Breakage Syndrome, Prague, Czech republic, 2002
Cybulski C, Górski B, Dębniak T, Gliniewicz B, Mierzejewski M, Masojć B, Jakubowska A, Matyjasik A, Złowocka E, Sikorki A, Narod SA, Lubiński J: NBS1 is a prostate cancer susceptibility gene. Cancer Res (in press) 2004
J Menkiszak B Górski A Jakubowska T Huzarski T Byrski J Gronwald M Foszczyńska-Kłoda O Haus H Janiszewska M Perkowska I Brożek E Grzybowska H Ziętek S Góźdź B Klonowska K Urbański R Miturski J Kowalczyk A Płużańska S Niepsuj J Koc M Szwiec K Drosik A Mackiewicz K Lamperska E Stróżyk D Godlewski M Stawicka B Waśko M Bębenek A Rozmiarek I Rzepka-Górska SA Narod J Lubiński (2003) ArticleTitleHereditary ovarian cancer in Poland Int J Cancer 106 942–945
Thompson D, Easton D, the Breast Cancer Linkage Consortium: variation in BRCA1 cancer risks by mutation position. Cancer Epidemiol Biomarkers Prev 11: 329–336, 2002
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Górski, B., Cybulski, C., Huzarski, T. et al. Breast cancer predisposing alleles in Poland. Breast Cancer Res Treat 92, 19–24 (2005). https://doi.org/10.1007/s10549-005-1409-1
Issue Date:
DOI: https://doi.org/10.1007/s10549-005-1409-1