The AIB1 polyglutamine repeat does not modify breast cancer risk in BRCA1 and BRCA2 mutation carriers.
Spurdle AB,
Antoniou AC,
Kelemen L,
Holland H,
Peock S,
Cook MR,
Smith PL,
Greene MH,
Simard J,
Plourde M,
Southey MC,
Godwin AK,
Beck J,
Miron A,
Daly MB,
Santella RM,
Hopper JL,
John EM,
Andrulis IL,
Durocher F,
Struewing JP,
Easton DF,
Chenevix-Trench G;
Australian Breast Cancer Family Study;
Australian Jewish Breast Cancer Study;
Breast Cancer Family Registry;
Interdisciplinary Health Research International Team on Breast Cancer Susceptibility;
Kathleen Cunningham Foundation Consortium for Research into Familial Breast Cancer;
Epidemiological Study of Familial Breast Cancer Study Collaborators.
The Queensland Institute of Medical Research, Brisbane, Australia. Amanda.Spurdle@qimr.edu.au
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. (Cancer Epidemiol Biomarkers Prev 2006;15(1):76-9).
PMID: 16434590 [PubMed - indexed for MEDLINE]