Abstract
To investigate the contribution of a founder deletion in the CHEK2 gene to the burden of breast cancer in Poland we studied 4,454 women with breast cancer and 5,496 population controls. Cases and controls were genotyped for the presence of a 5,395 bp founder deletion that removes exons 9 and 10 of the CHEK2 gene. This deletion has recently been described in a Czech and Slovak population. The cases and controls had previously been tested for two protein-truncating (IVS2 + 1G > A and 1100delC) and one missense CHEK2 mutation (I157T) which are characteristic for the population. The exons 9 and 10 deletion was present in 0.4% of the controls, in 1.0% (19 of 1,978) of unselected breast cancer cases (OR=2.2; 95% CI: 1.2–4.0; p = 0.01) and in 0.9% (28 of 3,228) of the early-onset cases (OR=2.0; 95% CI: 1.3–1.8; p = 0.02). One of the three truncating CHEK2 mutations (del5395; 1100delC or IVS2 + 1G > A) was seen in 101 of 4,454 (2.3%) cases and in 58 of 5,496 controls (1.1%) (OR=2.2; 95% CI: 1.6–3.0 p < 0.0001). A 5,395 bp founder deletion contributes to the burden of breast cancer in Poland. The deletion was present in 0.9% of the women with breast cancer diagnosed under the age of 51 and in 0.9% of women with breast cancer over the age of 50. This is one of the most common protein-truncating CHEK2 variants in Poland. Overall, 2% of all breast cancers in Poland can be attributed to one of three protein-truncating mutatiosns in CHEK2.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Matsuoka S, Rotman G, Ogawa A, Shiloh Y, Tamai K, Elledge SJ (2000) Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro. Proc Natl Acad Sci USA 97:10389–10394
Chaturvedi P, Eng WK, Zhu Y et al. (1999) Mammalian Chk2 is a downstream effector of the ATM-dependent DNA damage checkpoint pathway. Oncogene 18:4047–4054
CHEK2 Breast Cancer Consortium (2002) Low-penetrance susceptibility to breast cancer due to CHEK2*1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet 31:55–59
Oldenburg RA, Kroeze-Jansema K, Kraan J et al. (2003) The CHEK2*1100delC variant acts as a breast cancer risk modifier in non-BRCA1/BRCA2 multiple-case families. Cancer Res 63:8153–8157
Vahteristo P, Bartkova J, Eerola H et al (2002) A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer. Am J Hum Genet 71:432–438
CHEK2 Breast Cancer Case–Control Consortium (2004) CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. Am J Hum Genet 74:1175–1182
Cybulski C, Gorski B, Huzarski T et al. (2004) CHEK2 is a multiorgan cancer susceptibility gene. Am J Hum Genet 75:1131–1135
Kilpivaara O, Vahteristo P, Falck J et al. (2004) CHEK2 variant I157T may be associated with increased breast cancer risk. Int J Cancer 111:543–547
Shaag A, Walsh T, Renbaum P et al. (2005) CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population. Hum Mol Genet 14:555–563
de Bock GH, Schutte M, Krol-Warmerdam EM et al. (2004) Tumour characteristics and prognosis of breast cancer patients carrying the germline CHEK2*1100delC variant. J Med Genet 41:731–735
Allinen M, Huusko P, Mantyniemi S, Launonen V, Winqvist R (2001) Mutation analysis of the CHK2 gene in families with hereditary breast cancer. Br J Cancer 85:209–212
Schutte M, Seal S, Barfoot R et al. (2003) Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility. Am J Hum Genet 72:1023–1028
Bogdanova N, Enssen-Dubrowinskaja N, Feshchenko S et al (2005) Association of two mutations in the CHEK2 gene with breast cancer. Int J Cancer 116:263–266
Gorski B, Cybulski C, Huzarski T et al. (2005) Breast cancer predisposing alleles in Poland. Breast Cancer Res Treat 92:19–24
Walsh T, Casadei S, Coats KH et al. (2006) Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA 295:1379–1388
Cybulski C, Huzarski T, Górski B et al (2004) A novel founder CHEK2 mutation is associated with increased prostate cancer risk. Cancer Res 64:2677–2679
Acknowledgements
We thank the following people who helped in this study: Uciński M., Grzybowska E., Lange D., Mika B., Mackiewicz A., Karczewska A., Breborowicz J., Lamperska K., Stawicka M., Gozdecka-Grodecka S., Bębenek M., Sorokin D., Wojnar A., Haus O., Sir J., Mierzwa T., Niepsuj S., Gugała K., Goźdź S., Sygut J., Kozak-Klonowska B., Musiatowicz B., Posmyk M., Kordek R., Morawiec M., Zambrano O., Waśko B., Fudali L., Surdyka D., Urbański K., Mituś J., Ryś J., Szwiec M., Rozmiarek A., Dziuba I., Wandzel P., Wiśniowski R., Szczylik C., Kozak A., Kozłowski A., Czajka R., Czeszyńska B., Dębniak B., Brembowicz G., Kalużewski B., Witek A., Skret A., Lenczewski A., Wonton J. and Gibaszek R.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cybulski, C., Wokołorczyk, D., Huzarski, T. et al. A deletion in CHEK2 of 5,395 bp predisposes to breast cancer in Poland. Breast Cancer Res Treat 102, 119–122 (2007). https://doi.org/10.1007/s10549-006-9320-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-006-9320-y