Polymorphisms in BRCA2 resulting in aberrant codon-usage and their analysis on familial breast cancer risk

  • Rongxi Yang
  • Bowang Chen
  • Kari Hemminki
  • Barbara Wappenschmidt
  • Christoph Engel
  • Christian Sutter
  • Nina Ditsch
  • Bernhard H. F. Weber
  • Dieter Niederacher
  • Norbert Arnold
  • Alfons Meindl
  • Claus R. Bartram
  • Rita K. Schmutzler
  • Barbara Burwinkel


Mutations in BRCA1 and BRCA2 are associated with increased breast cancer risk. While numerous non-synonymous SNPs in BRCA1/2 have been investigated for breast cancer risk, the impact of synonymous SNPs has not been studied so far. Recently, it has been reported that synonymous SNPs leading to an aberration from the preferred codon-usage can have functional effects and consequently be associated with disease. This motivated us to search for SNPs with the tendency to differential codon-usage in BRCA1/BRCA2. Based on defined criteria, two codon-usage-changing variants, Ser455Ser (1365A > G) and Ser2414Ser (7242A > G), were detected in BRCA2, whereas no such variant could be identified in BRCA1. We investigated the impact of these variants on breast cancer risk in a large case–control study. However, both SNPs, BRCA2 Ser2414Ser (7242A > G) and Ser455Ser (1365A > G), showed no association with breast cancer risk. This indicates that these codon-usage-changing SNPs have no major impact on familial breast cancer risk.


Breast cancer risk Case–control study Codon-usage BRCA1 BRCA2 



We would like to thank all participants who joined this study. The German breast cancer samples were collected within a project funded by the Deutsche Krebshilfe (Grant number: 107054). This study was supported by the Helmholtz society, the German Cancer Research Center (DKFZ) and the EU, LSHC-CT-2004-503465.


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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Rongxi Yang
    • 1
    • 2
  • Bowang Chen
    • 3
  • Kari Hemminki
    • 3
    • 4
  • Barbara Wappenschmidt
    • 5
    • 6
  • Christoph Engel
    • 7
  • Christian Sutter
    • 8
  • Nina Ditsch
    • 9
  • Bernhard H. F. Weber
    • 10
  • Dieter Niederacher
    • 11
  • Norbert Arnold
    • 12
  • Alfons Meindl
    • 13
  • Claus R. Bartram
    • 8
  • Rita K. Schmutzler
    • 5
    • 6
  • Barbara Burwinkel
    • 1
    • 2
  1. 1.Helmholtz-University Group Molecular EpidemiologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  2. 2.Division Molecular Biology of Breast Cancer, Department of Gynecology and ObstetricsUniversity of HeidelbergHeidelbergGermany
  3. 3.Division of Molecular Genetic EpidemiologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  4. 4.Department of Biosciences at NovumKarolinska InstituteHuddingeSweden
  5. 5.Division of Molecular Gynaeco-Oncology, Department of Gynaecology and ObstetricsClinical Center University of CologneKölnGermany
  6. 6.Center of Molecular Medicine Cologne (CMMC)University Hospital of CologneKölnGermany
  7. 7.Department of Medical Informatics, Statistics and EpidemiologyUniversity of LeipzigLeipzigGermany
  8. 8.Institute of Human GeneticsUniversity of HeidelbergHeidelbergGermany
  9. 9.Department for Obstetrics and GynaecologyLudwig Maximilians UniversitätMunichGermany
  10. 10.Institute of Human GeneticsUniversity of RegensburgRegensburgGermany
  11. 11.Division of Molecular Genetics, Department of Gynaecology and ObstetricsClinical Center University of DüsseldorfDüsseldorfGermany
  12. 12.Division of Oncology, Department of Gynaecology and ObstetricsUniversity Hospital Schleswig–HolsteinKielGermany
  13. 13.Department of Gynaecology and Obstetrics, Klinikum rechts der IsarTechnical University of MunichMunichGermany

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