Coverage of the Genetic Background of Breast Cancer in the Polish Population
© The Author(s) 2006
Received: 15 October 2005
Accepted: 15 November 2005
Published: 15 November 2006
KeywordsBRCA1 BRCA2 CHEK2 NOD2 p16 NBS1 breast cancer
It is a known fact that cancer risk is influenced by both environmental and genetic factors. Parameters such as the kind and site of the tumour and family history depend on the proportion between both and the population determines to a great extent the characteristics of the genetic background. Here we focus on breast cancer in the Polish population.
Despite complex population dynamics in the last centuries, the Poles seem to be surprisingly homogeneous in their genetics. A sequence-based screening of BRCA1 positive patients showed just 9 polymorphisms of BRCA1, where 91% of individuals shared just 3 common founder mutations . The result is consistent with other Slavic countries [2–4]. In contrast, a similar screening in neighbouring Germany revealed 77 distinct BRCA1 mutations, 18 of them shared by 68% of BRCA1 positive patients .
Highly penetrating mutations, such as those of BRCA1, are mostly detected in conspicuous family aggregations via genetic linkage studies. Therefore, they may be detected with the help of just a few families even in heterogeneous populations. However, the probability of finding a new highly penetrating gene for the Polish population seems rather low; mutations of BRCA1 and BRCA2 already cover ~70% of cases of strong familial aggregations of breast and ovarian cancers . The advantage of genetically homogeneous populations relies instead on the increased power of finding medium- and low-risk markers via large association studies that would otherwise be blurred in more complex populations.
Those values should drop for cases with onset at older ages as the cumulative exposure to external carcinogenic agents increases. Nevertheless, in familial aggregations of breast and ovarian cancer that percentage is expected to be higher since just BRCA1 and BRCA2 account already for almost 70% of cases. Both analyses have still to be performed.
The Polish population appears to be a useful group for detecting low-risk markers of cancer. It is large (~40 m) and homogeneous enough to reach the statistical power necessary to detect small but still significant differences in cancer risk. Our actual knowledge of disease-associated genetic factors present in breast cancer cases is ~70% for familial aggregations and ~80% for early onset consecutive cases. Thanks to the parallel growth of the network country-wide for sample and data exchange and the genetic variants under analysis, we expect to approach 100% in the near future.
The Polish Hereditary Cancer Consortium are (in alphabetical order)
International Hereditary Cancer Center. Połabska 4, 70115 Szczecin, Poland.
Department of Obstetrics and Perinatology, Pomeranian Medical University, Szczecin, Poland.
Department of Pathology, Pomeranian Medical University, Szczecin, Poland.
Inter-University Unit of Molecular Biology, University of Szczecin and Pomeranian Medical University, Szczecin, Poland.
Medical University of Silesia, Katowice, Poland.
Centre for Research on Women's Health, Toronto, Canada.
Clinic of Urology, Pomeranian Academy of Medicine, Szczecin, Poland.
Regional Oncology Hospital, Białystok, Poland.
Regional Oncology Hospital, Olsztyn, Poland.
Poznan Medical University, Poland.
Department of Clinical Genetics, Bydgoszcz Medical University, Poland.
Regional Oncology Center, Kraków, Poland.
Discipline of Medical Genetics, Faculty of Health, University of Newcastle, Hunter Medical Research Institute, NSW, Australia.
Department of Urology, Pomeranian Medical University, Szczecin, Poland.
Prophylactic and Epidemiology Center, Poznań, Poland.
Regional Oncology Hospital, Lublin, Poland.
Regional Oncology Hospital, Bielsko Biała, Poland.
- Gorski B, Jakubowska A, Huzarski T, Byrski T, Gronwald J, Grzybowska E, Mackiewicz A, Stawicka M, Bebenek M, Sorokin D, Fiszer-Maliszewska L, Haus O, Janiszewska H, Niepsuj S, Gozdz S, Zaremba L, Posmyk M, Pluzanska M, Kilar E, Czudowska D, Wasko B, Miturski R, Kowalczyk JR, Urbanski K, Szwiec M, Koc J, Debniak B, Rozmiarek A, Debniak T, Cybulski C, Kowalska E, Toloczko-Grabarek A, Zajaczek S, Menkiszak J, Medrek K, Masojc B, Mierzejewski M, Narod SA, Lubinski J: A high proportion of founder BRCA1 mutations in Polish breast cancer families. Int J Cancer 2004, 110: 683–686. 10.1002/ijc.20162View ArticlePubMedGoogle Scholar
- Machackova E, Foretova L, Navratilova M, Valik D, Claes K, Messiaen L: A high occurrence of BRCA1 and BRCA2 mutations among Czech hereditary breast and breast-ovarian cancer families. Cas Lek Cesk 2000, 139: 635–637.PubMedGoogle Scholar
- Csokay B, Tihomirova L, Stengrevics A, Sinicka O, Olah E: Strong founder effects in BRCA1 mutation carrier breast cancer patients from Latvia. Mutation in brief no. 258: Online. Hum Mutat 1999, 14: 92. 10.1002/(SICI)1098-1004(1999)14:1<92::AID-HUMU23>3.0.CO;2-2View ArticlePubMedGoogle 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
- Meindl A, German Consortium for Hereditary Breast and Ovarian Cancer: Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population. Int J Cancer 2002, 97: 472–480. 10.1002/ijc.1626View ArticlePubMedGoogle Scholar
- Gorski B, Cybulski C, Huzarski T, Byrski T, Gronwald J, Jakubowska A, Stawicka M, Gozdecka-Grodecka S, Szwiec M, Urbanski K, Mitus J, Marczyk E, Dziuba J, Wandzel P, Surdyka D, Haus O, Janiszewska H, Debniak T, Toloczko-Grabarek A, Medrek K, Masojc B, Mierzejewski M, Kowalska E, Narod SA, Lubinski J: Breast cancer predisposing alleles in Poland. Breast Cancer Res Treat 2005, 92: 19–24. 10.1007/s10549-005-1409-1View ArticlePubMedGoogle Scholar
- Huzarski T, Lener M, Domagala W, Gronwald J, Byrski T, Kurzawski G, Suchy J, Chosia M, Woyton J, Ucinski M, Narod SA, Lubinski J: The 3020insC allele of NOD2 predisposes to early-onset breast cancer. Breast Cancer Res Treat 2005, 89: 91–93. 10.1007/s10549-004-1250-yView ArticlePubMedGoogle Scholar
- Debniak T, Gorski B, Huzarski T, Byrski T, Cybulski C, Mackiewicz A, Gozdecka-Grodecka S, Gronwald J, Kowalska E, Haus O, Grzybowska E, Stawicka M, Swiec M, Urbanski K, Niepsuj S, Wasko B, Gozdz S, Wandzel P, Szczylik C, Surdyka D, Rozmiarek A, Zambrano O, Posmyk M, Narod SA, Lubinski J: A common variant of CDKN2A (p16) predisposes to breast cancer. J Med Genet 2005, 42: 763–765. 10.1136/jmg.2005.031476PubMed CentralView ArticlePubMedGoogle Scholar
- Cybulski C, Gorski B, Huzarski T, Masojc B, Mierzejewski M, Debniak T, Teodorczyk U, Byrski T, Gronwald J, Matyjasik J, Zlowocka E, Lenner M, Grabowska E, Nej K, Castaneda J, Medrek K, Szymanska A, Szymanska J, Kurzawski G, Suchy J, Oszurek O, Witek A, Narod SA, Lubinski J: CHEK2 is a multiorgan cancer susceptibility gene. Am J Hum Genet 2004, 75: 1131–1135. 10.1086/426403PubMed CentralView ArticlePubMedGoogle Scholar
- Lubinski J: Familial Cancer Epidemiology: Common and Rare Inherited Cancer Syndromes, Family Cancer Database, Madrid 06.05.2004, Conference of the European School of Oncology.Google Scholar