A case-control study of the androgen receptor gene CAG repeat polymorphism in Australian prostate carcinoma subjects.
BACKGROUND
The development of prostate carcinoma is androgen-dependent. The coding sequence of the androgen receptor (AR) gene contains a CAG repeat polymorphism that has been shown to influence AR activity in vitro. Studies of this polymorphism as a prostate carcinoma risk factor have been conflicting.


METHODS
A matched case-control design was used in a clinic-based multicenter study of Australian prostate carcinoma subjects. Cancer subjects were matched by age and locality with controls, all of whom had a serum prostate specific antigen (PSA) level of less than 4 mg/L. Conditional logistic regression was used to determine the relative risk of prostate carcinoma dependent on AR gene CAG number. The association of disease characteristics at diagnosis with the polymorphism also was assessed.


RESULTS
Five hundred forty-five cases of prostate carcinoma and 456 matched case-control pairs were recruited. Association studies of disease characteristics at diagnosis showed age at diagnosis to be associated with AR CAG number by univariate (P = 0.004) and multivariate (adjusting for PSA, stage, and grade) linear regression (P = 0.018). No association was observed between the polymorphism and disease stage (TNM-based categories; P = 0.277), histologic grade (P = 0.41), or PSA level at diagnosis (P = 0.48). In the pairwise case-control analysis, the odds ratio of prostate carcinoma for a change of 5 CAG repeats gave an odds ratio of 0.9821 (95% confidence interval, 0.84-1.15).


CONCLUSIONS
In this Australian study population, the AR CAG repeat polymorphism was not a risk factor for prostate carcinoma, but a shorter repeat sequence was associated with earlier age at diagnosis.
Beilin
J
J
Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia. jonathanbeilin@hotmail.com
Harewood
L
L
Frydenberg
M
M
Mameghan
H
H
Martyres
R F
RF
Farish
S J
SJ
Yue
C
C
Deam
D R
DR
Byron
K A
KA
Zajac
J D
JD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D016022:Case-Control Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics*; D012044:Regression Analysis; D012307:Risk Factors; D018911:Trinucleotide Repeats
D011944:Receptors, Androgen