Epidemiology

Breast Cancer Research and Treatment

, 118:407

First online:

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

  • Rongxi YangAffiliated withHelmholtz-University Group Molecular Epidemiology, German Cancer Research Center (DKFZ)Division Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg Email author 
  • , Bowang ChenAffiliated withDivision of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ)
  • , Kari HemminkiAffiliated withDivision of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ)Department of Biosciences at Novum, Karolinska Institute
  • , Barbara WappenschmidtAffiliated withDivision of Molecular Gynaeco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center University of CologneCenter of Molecular Medicine Cologne (CMMC), University Hospital of Cologne
  • , Christoph EngelAffiliated withDepartment of Medical Informatics, Statistics and Epidemiology, University of Leipzig
  • , Christian SutterAffiliated withInstitute of Human Genetics, University of Heidelberg
  • , Nina DitschAffiliated withDepartment for Obstetrics and Gynaecology, Ludwig Maximilians Universität
  • , Bernhard H. F. WeberAffiliated withInstitute of Human Genetics, University of Regensburg
  • , Dieter NiederacherAffiliated withDivision of Molecular Genetics, Department of Gynaecology and Obstetrics, Clinical Center University of Düsseldorf
    • , Norbert ArnoldAffiliated withDivision of Oncology, Department of Gynaecology and Obstetrics, University Hospital Schleswig–Holstein
    • , Alfons MeindlAffiliated withDepartment of Gynaecology and Obstetrics, Klinikum rechts der Isar, Technical University of Munich
    • , Claus R. BartramAffiliated withInstitute of Human Genetics, University of Heidelberg
    • , Rita K. SchmutzlerAffiliated withDivision of Molecular Gynaeco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center University of CologneCenter of Molecular Medicine Cologne (CMMC), University Hospital of Cologne
    • , Barbara BurwinkelAffiliated withHelmholtz-University Group Molecular Epidemiology, German Cancer Research Center (DKFZ)Division Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg

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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 risk Case–control study Codon-usage BRCA1 BRCA2