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Analysis of CHEK2 FHA domain in Czech patients with sporadic breast cancer revealed distinct rare genetic alterations

  • Epidemiology
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Abstract

The CHEK2 gene mutations I157T (c.470T > C) and IVS2 + 1G > A affecting the forkhead-associated domain (FHA) have been shown to increase the risk of breast cancer development in several populations. We analyzed the CHEK2 gene segment coding for FHA domain in 673 unselected breast cancer patients and 683 controls from the Czech Republic using the denaturant high-performance liquid chromatography. The found frequency of predominant FHA alteration I157T did not differ between breast cancer patients (19/673; 2.82%) and controls (17/683; 2.49%; P = 0.71). Besides this mutation we characterized another nine alterations—six located within FHA coding sequence and three occurring in introns 1 or 2). Eight variants occurred once each in patients with breast cancer and two were present in controls. Three alterations found in breast cancer patients were novel missense variants (Y159H, T172A, and L174F) affecting highly conservative residues in FHA domain. Despite the lack of association of I157T mutation with breast cancer development in our population we deduced that the FHA domain is the subject of rare population-specific alterations that might modify risk of various cancers.

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Acknowledgement

This work was supported by Research Project of the Ministry of Education, Youth and Sports of the Czech Republic No MSM0021620808. We thank, to Marie Epsteinova for technical help, to Ing. Stanislav Kormuda for statistical analyses, to Dr. Martin Mateju for help with clinical data management, and to our patients and volunteers for their collaboration.

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Authors and Affiliations

  1. Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, U Nemocnice 5, 128 53, Prague 2, Czech Republic

    Zdenek Kleibl, Petra Kleiblova & Petr Pohlreich

  2. 1st Medical Department, General Teaching Hospital, First Faculty of Medicine, Charles University in Prague, Prague 2, Czech Republic

    Ondrej Havranek

  3. Department of Oncology, General Teaching Hospital, First Faculty of Medicine, Charles University in Prague, Prague 2, Czech Republic

    Jan Novotny

  4. Group for Biotransformations, Center of Occupational Medicine, National Institute of Public Health, Prague 10, Czech Republic

    Pavel Soucek

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  1. Zdenek Kleibl
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  2. Ondrej Havranek
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  3. Jan Novotny
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  4. Petra Kleiblova
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  5. Pavel Soucek
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  6. Petr Pohlreich
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Correspondence to Zdenek Kleibl.

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Zdenek Kleibl, Ondrej Havranek contributed equally to this work.

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Kleibl, Z., Havranek, O., Novotny, J. et al. Analysis of CHEK2 FHA domain in Czech patients with sporadic breast cancer revealed distinct rare genetic alterations. Breast Cancer Res Treat 112, 159–164 (2008). https://doi.org/10.1007/s10549-007-9838-7

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  • DOI: https://doi.org/10.1007/s10549-007-9838-7

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