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

  • Amanda B. Spurdle
  • Andrew J. Deans
  • David Duffy
  • David E. Goldgar
  • Xiaoqing Chen
  • Jonathan Beesley
  • kConFaB
  • Douglas F. Easton
  • Antonis C. Antoniou
  • Susan Peock
  • Margaret Cook
  • EMBRACE Study Collaborators
  • Katherine L. Nathanson
  • Susan M. Domchek
  • Grant A. MacArthur
  • Georgia Chenevix-Trench
Preclinical Study

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 

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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Amanda B. Spurdle
    • 1
    • 2
  • Andrew J. Deans
    • 3
  • David Duffy
    • 1
  • David E. Goldgar
    • 4
  • Xiaoqing Chen
    • 1
  • Jonathan Beesley
    • 1
  • kConFaB
    • 5
  • Douglas F. Easton
    • 6
  • Antonis C. Antoniou
    • 6
  • Susan Peock
    • 6
  • Margaret Cook
    • 6
  • EMBRACE Study Collaborators
    • 6
  • Katherine L. Nathanson
    • 7
  • Susan M. Domchek
    • 7
  • Grant A. MacArthur
    • 3
    • 8
  • Georgia Chenevix-Trench
    • 1
  1. 1.Queensland Institute of Medical ResearchBrisbaneAustralia
  2. 2.Genetics and Population Health DivisionQueensland Institute of Medical ResearchHerstonAustralia
  3. 3.Peter MacCallum Cancer CentreMelbourneAustralia
  4. 4.Department of DermatologyUniversity of UtahSalt Lake CityUSA
  5. 5.The Kathleen Cunningham Foundation Consortium for Research into Familial Breast CancerPeter MacCallum Cancer CentreMelbourneAustralia
  6. 6.Cancer Research UK Genetic Epidemiology Unit, Department of Public Health and Primary CareUniversity of CambridgeCambridgeUK
  7. 7.Department of Medicine and Abramson Cancer CenterUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  8. 8.Department of MedicineSt Vincents HopsitalMelbourneAustralia

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