Polymorphisms in genes involved in sex hormone metabolism may increase risk of benign prostatic hyperplasia

Rosebud O Roberts, Erik J. Bergstralh, Sara A. Farmer, Debra J. Jacobson, Scott J. Hebbring, Julie M Cunningham, Stephen N Thibodeau, Michael M. Lieber, Steven J. Jacobsen

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)392-404
Number of pages13
JournalProstate
Volume66
Issue number4
DOIs
StatePublished - Mar 1 2006

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Prostatic Hyperplasia
Gonadal Steroid Hormones
Prostate
Confidence Intervals
Aromatase
Genotype
Genes
Prostate-Specific Antigen
Independent Living
Lower Urinary Tract Symptoms
Urinary Retention
Longitudinal Studies
Multivariate Analysis
Therapeutics
Serum

Keywords

  • Flow rates
  • Genetics
  • Polymorphisms
  • Prostate
  • Prostatic hyperplasia
  • Symptoms
  • Treatment

ASJC Scopus subject areas

  • Urology

Cite this

Roberts, R. O., Bergstralh, E. J., Farmer, S. A., Jacobson, D. J., Hebbring, S. J., Cunningham, J. M., ... Jacobsen, S. J. (2006). Polymorphisms in genes involved in sex hormone metabolism may increase risk of benign prostatic hyperplasia. Prostate, 66(4), 392-404. https://doi.org/10.1002/pros.20362

Polymorphisms in genes involved in sex hormone metabolism may increase risk of benign prostatic hyperplasia. / Roberts, Rosebud O; Bergstralh, Erik J.; Farmer, Sara A.; Jacobson, Debra J.; Hebbring, Scott J.; Cunningham, Julie M; Thibodeau, Stephen N; Lieber, Michael M.; Jacobsen, Steven J.

In: Prostate, Vol. 66, No. 4, 01.03.2006, p. 392-404.

Research output: Contribution to journalArticle

Roberts, RO, Bergstralh, EJ, Farmer, SA, Jacobson, DJ, Hebbring, SJ, Cunningham, JM, Thibodeau, SN, Lieber, MM & Jacobsen, SJ 2006, 'Polymorphisms in genes involved in sex hormone metabolism may increase risk of benign prostatic hyperplasia', Prostate, vol. 66, no. 4, pp. 392-404. https://doi.org/10.1002/pros.20362
Roberts, Rosebud O ; Bergstralh, Erik J. ; Farmer, Sara A. ; Jacobson, Debra J. ; Hebbring, Scott J. ; Cunningham, Julie M ; Thibodeau, Stephen N ; Lieber, Michael M. ; Jacobsen, Steven J. / Polymorphisms in genes involved in sex hormone metabolism may increase risk of benign prostatic hyperplasia. In: Prostate. 2006 ; Vol. 66, No. 4. pp. 392-404.
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abstract = "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.",
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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

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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

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KW - Prostate

KW - Prostatic hyperplasia

KW - Symptoms

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