The CAG repeat within the androgen receptor gene and benign prostatic hyperplasia.
OBJECTIVE
Shorter CAG repeat lengths in exon 1 of the androgen receptor (AR) gene are associated with a stronger transcriptional activity of the AR and with a higher risk of prostate cancer. Because benign prostatic hyperplasia (BPH) is an androgen-dependent condition, we examined the hypothesis that men with shorter AR gene CAG repeat lengths have an increased risk of developing BPH.


METHODS
Using data from the Health Professionals Follow-up Study (HPFS), we evaluated the relationship between AR gene CAG repeat length and prevalent BPH, as defined by BPH surgery, by enlarged prostate gland detected by digital rectal examination, and by urinary symptoms as determined by the American Urological Association Symptom Index.


RESULTS
The odds ratio for BPH surgery or enlarged prostate gland was 1.92 (95% confidence interval [CI] 1.22 to 3.03; P [trend] = 0.0002), comparing AR gene CAG repeat length of 1 9 or less to 25 or more. Results were similar for the end points of BPH surgery (P [trend] = 0.002) and for enlarged prostate gland (P [trend] = 0.001). For a six-repeat decrease in CAG repeat length, the odds ratio for having moderate or severe urinary obstructive symptoms from an enlarged prostate gland was 3.62 (95% CI 1.51 to 8.67; P = 0.004).


CONCLUSIONS
Variability in the AR gene CAG repeat influences the development of symptomatic BPH, particularly in predicting obstructive urinary symptoms. Our findings support further study to establish the appropriate clinical relevance.
Giovannucci
E
E
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Platz
E A
EA
Stampfer
M J
MJ
Chan
A
A
Krithivas
K
K
Kawachi
I
I
Willett
W C
WC
Kantoff
P W
PW
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011470:Prostatic Hyperplasia / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics*; D018911:Trinucleotide Repeats
D011944:Receptors, Androgen