Author/Authors :
R.O. Roberts، نويسنده , , E.J. Bergstralh، نويسنده , , S.A. Farmer، نويسنده , , D.J. Jacobson، نويسنده , , S.J. Hebbring، نويسنده , , J.M. Cunningham، نويسنده , , S.N. Thibodeau، نويسنده , , M.M. Lieber، نويسنده , , S.J. Jacobsen، نويسنده ,
Abstract :
Purpose
Because sex hormones are involved in the development of benign prostatic hyperplasia (BPH), we examined associations between polymorphisms in genes involved in androgen and estrogen metabolism and measures of BPH.
Methods
A cohort of 510 community-dwelling Caucasian men (median age 60 years in 2000), randomly selected from the Olmsted County, MN population, participated in a longitudinal study of BPH. From 1990 through 2000, urologic measures of BPH were assessed biennially, including lower urinary tract symptom severity, peak urinary flow rates, prostate volume, and serum prostate specific antigen (PSA) level. Acute urinary retention and treatment for BPH were assessed from community medical records. Men were genotyped for candidate genes involved in androgen and estrogen metabolism.
Results
With the wildtype genotype as reference, significant associations (p < 0.01) were observed between HSD3B1 AC heterozygous genotype and risk of an enlarged prostate (Hazard Ratio (HR) = 0.7, 95% Confidence intervals (CI) = 0.6, 0.9), CYP19 genotype homozygous for ≥ 175 TTTA repeats and an enlarged prostate (HR = 1.5, 95% CI = 1.1, 2.1), CYP19 homozygous variant TT genotype and an enlarged prostate (HR = 1.6, 95% CI = 1.1, 2.2). ARE1 (-252 G_A) homozygous AA genotype was associated with medical treatment for BPH (HR = 2.3, 95% CI = 1.2, 4.4). The risk (HR, 95% CI) of an enlarged prostate was increased in men with 2 high risk genotypes for HSD3B1 (1.4 [1.0, 1.8]) and CYP19 (1.8 [1.3, 2.3]) and ≥2 high risk ARE1 genotypes was associated with an increased risk of treatment for BPH (2.9 [1.4, 5.8]).
Conclusion
These findings suggest possible associations between HSD3B1, CYP19, and ARE1 gene polymorphisms and measures of BPH. While no one polymorphism is associated uniformly across surrogate measures of BPH, these data suggest that further examination of these genes for their potential role in the etiology, diagnosis, prevention, or treatment of BPH may be warranted.
