Breast Cancer Research and Treatment

, 118:407

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

Authors

    • Helmholtz-University Group Molecular EpidemiologyGerman Cancer Research Center (DKFZ)
    • Division Molecular Biology of Breast Cancer, Department of Gynecology and ObstetricsUniversity of Heidelberg
  • Bowang Chen
    • Division of Molecular Genetic EpidemiologyGerman Cancer Research Center (DKFZ)
  • Kari Hemminki
    • Division of Molecular Genetic EpidemiologyGerman Cancer Research Center (DKFZ)
    • Department of Biosciences at NovumKarolinska Institute
  • Barbara Wappenschmidt
    • Division of Molecular Gynaeco-Oncology, Department of Gynaecology and ObstetricsClinical Center University of Cologne
    • Center of Molecular Medicine Cologne (CMMC)University Hospital of Cologne
  • Christoph Engel
    • Department of Medical Informatics, Statistics and EpidemiologyUniversity of Leipzig
  • Christian Sutter
    • Institute of Human GeneticsUniversity of Heidelberg
  • Nina Ditsch
    • Department for Obstetrics and GynaecologyLudwig Maximilians Universität
  • Bernhard H. F. Weber
    • Institute of Human GeneticsUniversity of Regensburg
  • Dieter Niederacher
    • Division of Molecular Genetics, Department of Gynaecology and ObstetricsClinical Center University of Düsseldorf
  • Norbert Arnold
    • Division of Oncology, Department of Gynaecology and ObstetricsUniversity Hospital Schleswig–Holstein
  • Alfons Meindl
    • Department of Gynaecology and Obstetrics, Klinikum rechts der IsarTechnical University of Munich
  • Claus R. Bartram
    • Institute of Human GeneticsUniversity of Heidelberg
  • Rita K. Schmutzler
    • Division of Molecular Gynaeco-Oncology, Department of Gynaecology and ObstetricsClinical Center University of Cologne
    • Center of Molecular Medicine Cologne (CMMC)University Hospital of Cologne
  • Barbara Burwinkel
    • Helmholtz-University Group Molecular EpidemiologyGerman Cancer Research Center (DKFZ)
    • Division Molecular Biology of Breast Cancer, Department of Gynecology and ObstetricsUniversity of Heidelberg
Epidemiology

DOI: 10.1007/s10549-009-0348-7

Cite this article as:
Yang, R., Chen, B., Hemminki, K. et al. Breast Cancer Res Treat (2009) 118: 407. doi:10.1007/s10549-009-0348-7

Abstract

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.

Keywords

Breast cancer riskCase–control studyCodon-usageBRCA1BRCA2

Copyright information

© Springer Science+Business Media, LLC. 2009