A comprehensive analysis of the androgen receptor gene and risk of breast cancer: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3).
BACKGROUND
Androgens have been hypothesised to influence risk of breast cancer through several possible mechanisms, including their conversion to estradiol or their binding to the oestrogen receptor and/or androgen receptor (AR) in the breast. Here, we report on the results of a large and comprehensive study of the association between genetic variation in the AR gene and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3).


METHODS
The underlying genetic variation was determined by first sequencing the coding regions of the AR gene in a panel of 95 advanced breast cancer cases. Second, a dense set of markers from the public database was genotyped in a panel of 349 healthy women. The linkage disequilibrium relationships (blocks) across the gene were then identified, and haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected to capture the common genetic variation across the locus. The htSNPs were then genotyped in the nested breast cancer cases and controls from the Cancer Prevention Study II, European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort, Nurses' Health Study, and Women's Health Study cohorts (5,603 breast cancer cases and 7,480 controls).


RESULTS
We found no association between any genetic variation (SNP, haplotype, or the exon 1 CAG repeat) in the AR gene and risk of breast cancer, nor were any statistical interactions with known breast cancer risk factors observed.


CONCLUSIONS
Among postmenopausal Caucasian women, common variants of the AR gene are not associated with risk of breast cancer.
Cox
David G
DG
Program in Molecular and Genetic Epidemiology, Epidemiology Department, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. dcox@hsph.harvard.edu
Blanché
Hélène
H
Pearce
Celeste L
CL
Calle
Eugenia E
EE
Colditz
Graham A
GA
Pike
Malcolm C
MC
Albanes
Demetrius
D
Allen
Naomi E
NE
Amiano
Pilar
P
Berglund
Goran
G
Boeing
Heiner
H
Buring
Julie
J
Burtt
Noel
N
Canzian
Federico
F
Chanock
Stephen
S
Clavel-Chapelon
Françoise
F
Feigelson
Heather Spencer
HS
Freedman
Matthew
M
Haiman
Christopher A
CA
Hankinson
Susan E
SE
Henderson
Brian E
BE
Hoover
Robert
R
Hunter
David J
DJ
Kaaks
Rudolf
R
Kolonel
Laurence
L
Kraft
Peter
P
LeMarchand
Loic
L
Lund
Eiliv
E
Palli
Domenico
D
Peeters
Petra H M
PH
Riboli
Elio
E
Stram
Daniel O
DO
Thun
Michael
M
Tjonneland
Anne
A
Trichopoulos
Dimitrios
D
Yeager
Meredith
M
D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011944:Receptors, Androgen / Q000235:genetics*; D012306:Risk
D011944:Receptors, Androgen