TY - JOUR
T1 - Polymorphisms in genes involved in sex hormone metabolism may increase risk of benign prostatic hyperplasia
AU - Roberts, Rosebud O.
AU - Bergstralh, Erik J.
AU - Farmer, Sara A.
AU - Jacobson, Debra J.
AU - Hebbring, Scott J.
AU - Cunningham, Julie M.
AU - Thibodeau, Stephen N.
AU - Lieber, Michael M.
AU - Jacobsen, Steven J.
PY - 2006/3/1
Y1 - 2006/3/1
N2 - BACKGROUND. This study investigates associations between polymorphisms in genes involved in sex hormone metabolism and measures of benign prostatic hyperplasia (BPH). METHOD S. Community-dwelling Caucasian men (n = 510, median age 60 years in 2000) from the Olmsted County, MN, participated in a longitudinal study of BPH. From 1990 through 2000, urologic measures of BPH were assessed biennially from lower urinary tract symptom severity, peak flow rates, prostate volume, serum prostate specific antigen (PSA) level, acute urinary retention, and treatment for BPH. Men were genotyped for polymorphisms in genes involved in sex hormone metabolism. RESULTS. With the wildtype genotype as reference, men with HSD3B1 (c.1100 A/C) heterozygous genotype (hazard ratio (HR) = 0.7, 95% confidence intervals (CI) = 0.6, 0.9) were at decreased risk of an enlarged prostate and men with CYP19 (TTTA)n genotype homozygous for ≥175 TTTA repeats (HR = 1.5, 95% CI = 1.1, 2.1), and CYP19 (c.1531 C/T) homozygous T variant (HR = 1.6, 95% CI = 1.1, 2.2) were at increased risk of an enlarged prostate. The homozygous A variant of the PSA gene (g.-252 G/A), was associated with treatment for BPH (HR = 2.3, 95% CI = 1.2, 4.4). In multivariate analyses, the homozygous variant genotypes of AKR1C3 (c.15 G/A and c.90 G/A) were associated with a decreased risk of an enlarged prostate (HR = 0.56, 95% CI = 0.35, 0.90 and HR = 0.57, 95% CI = 0.33, 0.98). CONCLUSIONS. Polymorphisms in HSD3B1, CYP19, AKR1C3 genes may be associated with an enlarged prostate in older men. These data provide insights into genes that should be examined further for their potential role in the pathogenesis of BPH.
AB - BACKGROUND. This study investigates associations between polymorphisms in genes involved in sex hormone metabolism and measures of benign prostatic hyperplasia (BPH). METHOD S. Community-dwelling Caucasian men (n = 510, median age 60 years in 2000) from the Olmsted County, MN, participated in a longitudinal study of BPH. From 1990 through 2000, urologic measures of BPH were assessed biennially from lower urinary tract symptom severity, peak flow rates, prostate volume, serum prostate specific antigen (PSA) level, acute urinary retention, and treatment for BPH. Men were genotyped for polymorphisms in genes involved in sex hormone metabolism. RESULTS. With the wildtype genotype as reference, men with HSD3B1 (c.1100 A/C) heterozygous genotype (hazard ratio (HR) = 0.7, 95% confidence intervals (CI) = 0.6, 0.9) were at decreased risk of an enlarged prostate and men with CYP19 (TTTA)n genotype homozygous for ≥175 TTTA repeats (HR = 1.5, 95% CI = 1.1, 2.1), and CYP19 (c.1531 C/T) homozygous T variant (HR = 1.6, 95% CI = 1.1, 2.2) were at increased risk of an enlarged prostate. The homozygous A variant of the PSA gene (g.-252 G/A), was associated with treatment for BPH (HR = 2.3, 95% CI = 1.2, 4.4). In multivariate analyses, the homozygous variant genotypes of AKR1C3 (c.15 G/A and c.90 G/A) were associated with a decreased risk of an enlarged prostate (HR = 0.56, 95% CI = 0.35, 0.90 and HR = 0.57, 95% CI = 0.33, 0.98). CONCLUSIONS. Polymorphisms in HSD3B1, CYP19, AKR1C3 genes may be associated with an enlarged prostate in older men. These data provide insights into genes that should be examined further for their potential role in the pathogenesis of BPH.
KW - Flow rates
KW - Genetics
KW - Polymorphisms
KW - Prostate
KW - Prostatic hyperplasia
KW - Symptoms
KW - Treatment
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U2 - 10.1002/pros.20362
DO - 10.1002/pros.20362
M3 - Article
C2 - 16302261
AN - SCOPUS:33644748551
SN - 0270-4137
VL - 66
SP - 392
EP - 404
JO - Prostate
JF - Prostate
IS - 4
ER -