No evidence that CDKN1B (p27) polymorphisms modify breast cancer risk in BRCA1 and BRCA2 mutation carriers.
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.
Spurdle
Amanda B
AB
Queensland Institute of Medical Research, Brisbane, Australia. amanda.spurdle@qimr.edu.au
Deans
Andrew J
AJ
Duffy
David
D
Goldgar
David E
DE
Chen
Xiaoqing
X
Beesley
Jonathan
J
Easton
Douglas F
DF
Antoniou
Antonis C
AC
Peock
Susan
S
Cook
Margaret
M
Nathanson
Katherine L
KL
Domchek
Susan M
SM
MacArthur
Grant A
GA
Chenevix-Trench
Georgia
G
D001943:Breast Neoplasms / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27