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Breast Cancer Research and Treatment

, Volume 117, Issue 1, pp 161–165 | Cite as

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

  • Pablo Serrano-Fernández
  • Tadeusz Dębniak
  • Bohdan Górski
  • Natalia Bogdanova
  • Thilo Dörk
  • Cezary Cybulski
  • Tomasz Huzarski
  • Tomasz Byrski
  • Jacek Gronwald
  • Dominika Wokołorczyk
  • Steven A. Narod
  • Jan Lubiński
Epidemiology

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.

Keywords

Breast cancer CHEK2 BRCA2 Breast cancer Gene interaction 

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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Pablo Serrano-Fernández
    • 1
  • Tadeusz Dębniak
    • 1
  • Bohdan Górski
    • 1
  • Natalia Bogdanova
    • 2
    • 3
    • 4
  • Thilo Dörk
    • 2
  • Cezary Cybulski
    • 1
  • Tomasz Huzarski
    • 1
  • Tomasz Byrski
    • 1
  • Jacek Gronwald
    • 1
  • Dominika Wokołorczyk
    • 1
  • Steven A. Narod
    • 5
  • Jan Lubiński
    • 1
  1. 1.International Hereditary Cancer Center, Department of Genetics and PathologyPomeranian Medical UniversitySzczecinPoland
  2. 2.Department of Obstetrics and GynaecologyHannover Medical SchoolHannoverGermany
  3. 3.Department of Radiation OncologyHannover Medical SchoolHannoverGermany
  4. 4.NN Alexandrov Research Institute of Oncology and Medical RadiologyMinskBelarus
  5. 5.Womens College Research InstituteTorontoCanada

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