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01-05-2009 | Preclinical Study

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

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

Published in: Breast Cancer Research and Treatment | Issue 2/2009

Abstract

The p27^kip1 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.

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Title: No evidence that CDKN1B (p27) polymorphisms modify breast cancer risk in BRCA1 and BRCA2 mutation carriers
Authors: Amanda B. Spurdle
Andrew J. Deans
David Duffy
David E. Goldgar
Xiaoqing Chen
Jonathan Beesley
Douglas F. Easton
Antonis C. Antoniou
Susan Peock
Margaret Cook
Katherine L. Nathanson
Susan M. Domchek
Grant A. MacArthur
Georgia Chenevix-Trench
kConFaB
EMBRACE Study Collaborators
Publication date: 01-05-2009
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 2/2009
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-008-0083-5

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