Breast Cancer Research and Treatment

, Volume 115, Issue 2, pp 307–313

No evidence that CDKN1B (p27) polymorphisms modify breast cancer risk in BRCA1 and BRCA2 mutation carriers

Authors

    • Queensland Institute of Medical Research
    • Genetics and Population Health DivisionQueensland Institute of Medical Research
  • Andrew J. Deans
    • Peter MacCallum Cancer Centre
  • David Duffy
    • Queensland Institute of Medical Research
  • David E. Goldgar
    • Department of DermatologyUniversity of Utah
  • Xiaoqing Chen
    • Queensland Institute of Medical Research
  • Jonathan Beesley
    • Queensland Institute of Medical Research
  • kConFaB
    • The Kathleen Cunningham Foundation Consortium for Research into Familial Breast CancerPeter MacCallum Cancer Centre
  • Douglas F. Easton
    • Cancer Research UK Genetic Epidemiology Unit, Department of Public Health and Primary CareUniversity of Cambridge
  • Antonis C. Antoniou
    • Cancer Research UK Genetic Epidemiology Unit, Department of Public Health and Primary CareUniversity of Cambridge
  • Susan Peock
    • Cancer Research UK Genetic Epidemiology Unit, Department of Public Health and Primary CareUniversity of Cambridge
  • Margaret Cook
    • Cancer Research UK Genetic Epidemiology Unit, Department of Public Health and Primary CareUniversity of Cambridge
  • EMBRACE Study Collaborators
    • Cancer Research UK Genetic Epidemiology Unit, Department of Public Health and Primary CareUniversity of Cambridge
  • Katherine L. Nathanson
    • Department of Medicine and Abramson Cancer CenterUniversity of Pennsylvania School of Medicine
  • Susan M. Domchek
    • Department of Medicine and Abramson Cancer CenterUniversity of Pennsylvania School of Medicine
  • Grant A. MacArthur
    • Peter MacCallum Cancer Centre
    • Department of MedicineSt Vincents Hopsital
  • Georgia Chenevix-Trench
    • Queensland Institute of Medical Research
Preclinical Study

DOI: 10.1007/s10549-008-0083-5

Cite this article as:
Spurdle, A.B., Deans, A.J., Duffy, D. et al. Breast Cancer Res Treat (2009) 115: 307. doi:10.1007/s10549-008-0083-5

Abstract

The p27kip1 protein functions as an inhibitor of cyclin dependent kinase-2, and shows loss of expression in a large percentage of BRCA1 and BRCA2 breast cancer cases. We investigated the association between CDKN1B gene variants and breast cancer risk in 2359 female BRCA1 and BRCA2 mutation carriers from Australia, the UK, and the USA. Samples were genotyped for five single nucleotide polymorphisms, including coding variant rs2066827 (V109G). Cox regression provided no convincing evidence that any of the polymorphisms modified disease risk for BRCA1 or BRCA2 carriers, either alone or as a haplotype. Borderline associations were observed for homozygote carriers of the rs3759216 rare allele, but were opposite in effect for BRCA1 and BRCA2 carriers (adjusted hazard ratio (HR) 0.72 (95% CI = 0.53–0.99; P = 0.04 for BRCA1, HR 1.47 (95% CI = 0.99–2.18; P = 0.06 for BRCA2). The 95% confidence intervals for per allele risk estimates excluded a twofold risk, indicating that common CDKN1B polymorphisms do not markedly modify breast cancer risk among BRCA1 or BRCA2 carriers.

Keywords

P27 BRCA1 BRCA2 Modifier

Copyright information

© Springer Science+Business Media, LLC. 2008