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Springer, Breast Cancer Research and Treatment, 2(115), p. 307-313, 2008

DOI: 10.1007/s10549-008-0083-5

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

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

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. Amanda B. Spurdle1, 2 , Andrew J. Deans3, David Duffy1, David E. Goldgar4, Xiaoqing Chen1, Jonathan Beesley1, kConFaB5, Douglas F. Easton6, Antonis C. Antoniou6, Susan Peock6, Margaret Cook6, EMBRACE Study Collaborators6, Katherine L. Nathanson7, Susan M. Domchek7, Grant A. MacArthur3, 8 and Georgia Chenevix-Trench1