The AIB1 polyglutamine repeat does not modify breast cancer risk in BRCA1 and BRCA2 mutation carriers.
This is by far the largest study of its kind to date, and further suggests that AIB1 does not play a substantial role in modifying the phenotype of BRCA1 and BRCA2 carriers. The AIB1 gene encodes the AIB1/SRC-3 steroid hormone receptor coactivator, and amplification of the gene and/or protein occurs in breast and ovarian tumors. A CAG/CAA repeat length polymorphism encodes a stretch of 17 to 29 glutamines in the HR-interacting carboxyl-terminal region of the protein which is somatically unstable in tumor tissues and cell lines. There is conflicting evidence regarding the role of this polymorphism as a modifier of breast cancer risk in BRCA1 and BRCA2 carriers. To further evaluate the evidence for an association between AIB1 glutamine repeat length and breast cancer risk in BRCA1 and BRCA2 mutation carriers, we have genotyped this polymorphism in 1,090 BRCA1 and 661 BRCA2 mutation carriers from Australia, Europe, and North America. There was no evidence for an increased risk associated with AIB1 glutamine repeat length. Given the large sample size, with more than adequate power to detect previously reported effects, we conclude that the AIB1 glutamine repeat does not substantially modify risk of breast cancer in BRCA1 and BRCA2 mutation carriers.
Spurdle
Amanda B
AB
The Queensland Institute of Medical Research, Brisbane, Australia. Amanda.Spurdle@qimr.edu.au
Antoniou
Antonis C
AC
Kelemen
Livia
L
Holland
Helene
H
Peock
Susan
S
Cook
Margaret R
MR
Smith
Paula L
PL
Greene
Mark H
MH
Simard
Jacques
J
Plourde
Marie
M
Southey
Melissa C
MC
Godwin
Andrew K
AK
Beck
Jeanne
J
Miron
Alexander
A
Daly
Mary B
MB
Santella
Regina M
RM
Hopper
John L
JL
John
Esther M
EM
Andrulis
Irene L
IL
Durocher
Francine
F
Struewing
Jeffery P
JP
Easton
Douglas F
DF
Chenevix-Trench
Georgia
G
D000123:Acetyltransferases / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051548:Histone Acetyltransferases; D006801:Humans; D009154:Mutation; D056921:Nuclear Receptor Coactivator 3; D015513:Oncogene Proteins / Q000235:genetics*; D010455:Peptides / Q000235:genetics*; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D012091:Repetitive Sequences, Nucleic Acid; D012306:Risk; D015534:Trans-Activators / Q000235:genetics*
D015513:Oncogene Proteins; D010455:Peptides; D015534:Trans-Activators; C097188:polyglutamine; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3