The androgen receptor CAG repeat polymorphism and modification of breast cancer risk in BRCA1 and BRCA2 mutation carriers.
BACKGROUND
The androgen receptor (AR) gene exon 1 CAG repeat polymorphism encodes a string of 9-32 glutamines. Women with germline BRCA1 mutations who carry at least one AR allele with 28 or more repeats have been reported to have an earlier age at onset of breast cancer.


METHODS
A total of 604 living female Australian and British BRCA1 and/or BRCA2 mutation carriers from 376 families were genotyped for the AR CAG repeat polymorphism. The association between AR genotype and disease risk was assessed using Cox regression. AR genotype was analyzed as a dichotomous covariate using cut-points previously reported to be associated with increased risk among BRCA1 mutation carriers, and as a continuous variable considering smaller allele, larger allele and average allele size.


RESULTS
There was no evidence that the AR CAG repeat polymorphism modified disease risk in the 376 BRCA1 or 219 BRCA2 mutation carriers screened successfully. The rate ratio associated with possession of at least one allele with 28 or more CAG repeats was 0.74 (95% confidence interval 0.42-1.29; P = 0.3) for BRCA1 carriers, and 1.12 (95% confidence interval 0.55-2.25; P = 0.8) for BRCA2 carriers.


CONCLUSIONS
The AR exon 1 CAG repeat polymorphism does not appear to have an effect on breast cancer risk in BRCA1 or BRCA2 mutation carriers.
Spurdle
Amanda B
AB
Queensland Institute of Medical Research, Brisbane, Australia. mandyS@qimr.edu.au
Antoniou
Antonis C
AC
Duffy
David L
DL
Pandeya
Nirmala
N
Kelemen
Livia
L
Chen
Xiaoqing
X
Peock
Susan
S
Cook
Margaret R
MR
Smith
Paula L
PL
Purdie
David M
DM
Newman
Beth
B
Dite
Gillian S
GS
Apicella
Carmel
C
Southey
Melissa C
MC
Giles
Graham G
GG
Hopper
John L
JL
Chenevix-Trench
Georgia
G
Easton
Douglas F
DF
D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011944:Receptors, Androgen / Q000235:genetics*; D018570:Risk Assessment; D018911:Trinucleotide Repeats / Q000235:genetics
D011944:Receptors, Androgen
Hum Mol Genet. 2000 Jan 22;9(2):267-74
10607837
Am J Hum Genet. 1999 Aug;65(2):567-9
10417300
Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11256-61
11016951
Cancer Res. 2000 Nov 1;60(21):5946-9
11085509
Br J Cancer. 2001 Jul 6;85(1):36-40
11437399
Eur J Hum Genet. 2002 Nov;10(11):724-8
12404104
Am J Hum Genet. 2003 May;72(5):1117-30
12677558
Breast Cancer Res. 2003;5(3):164-73
12793900
Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7201-6
12756300
Breast Cancer Res. 2003;5(6):R206-16
14580256
Nat Genet. 1992 Oct;2(2):132-4
1303262
Nat Genet. 1993 Oct;5(2):109-10
8252034
Nucleic Acids Res. 1994 Aug 11;22(15):3181-6
8065934
Int J Cancer. 1997 Aug 7;72(4):574-80
9259393
Cancer Causes Control. 1998 Mar;9(2):189-98
9578296
Am J Hum Genet. 1999 May;64(5):1371-7
10205268
J Natl Cancer Inst. 1999 Jun 2;91(11):961-6
10359549
J Natl Cancer Inst Monogr. 1999;(26):95-100
10854492