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Synergistic interaction of variants in CHEK2 and BRCA2 on breast cancer risk

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

We studied the effects of BRCA2 and CHEK2 variants on breast cancer risk in two case-control series from Poland and Belarus. The missense BRCA2 variant T1915M was associated with a significant reduction in breast cancer risk (OR = 0.62; 95% CI 0.49–0.79; P = 0.0007). Modest increases of breast cancer risk were observed for the four analysed CHEK2 variants (I157T, 1100delC, IVS2 + 1G > A and del5395) (OR = 2.2; 95% 1.7–2.8; P = 0.0001). The highest risk was observed among women who carried both a BRCA2 and a CHEK2 variant (OR = 5.7; 95% CI 1.7–19; P = 0.006). We observed a statistically significant interaction effect between CHEK2 mutations and the BRCA2 substitution (P = 0.03). These data suggest that the BRCA2 T1915M polymorphism alone might be associated with a reduced risk of breast cancer, but among CHEK2 mutation carriers, it may lead to an unexpectedly high risk.

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Notes

  1. Cybulski C, Huzarski T, Byrski T, Lubiński J. Estrogen Receptor Status in CHEK2-positive Breast Cancers: Implications for Chemoprevention (submitted for publication).

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Authors and Affiliations

  1. International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, ul. Połabska 4, 70-115, Szczecin, Poland

    Pablo Serrano-Fernández, Tadeusz Dębniak, Bohdan Górski, Cezary Cybulski, Tomasz Huzarski, Tomasz Byrski, Jacek Gronwald, Dominika Wokołorczyk & Jan Lubiński

  2. Department of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany

    Natalia Bogdanova & Thilo Dörk

  3. Department of Radiation Oncology, Hannover Medical School, Hannover, Germany

    Natalia Bogdanova

  4. NN Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus

    Natalia Bogdanova

  5. Womens College Research Institute, Toronto, ON, Canada

    Steven A. Narod

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  1. Pablo Serrano-Fernández
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  2. Tadeusz Dębniak
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  3. Bohdan Górski
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  4. Natalia Bogdanova
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  6. Cezary Cybulski
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  7. Tomasz Huzarski
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  10. Dominika Wokołorczyk
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  11. Steven A. Narod
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  12. Jan Lubiński
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Correspondence to Pablo Serrano-Fernández.

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Serrano-Fernández, P., Dębniak, T., Górski, B. et al. Synergistic interaction of variants in CHEK2 and BRCA2 on breast cancer risk. Breast Cancer Res Treat 117, 161–165 (2009). https://doi.org/10.1007/s10549-008-0249-1

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  • DOI: https://doi.org/10.1007/s10549-008-0249-1

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