Genetic Polymorphisms Benign Prostatic Hyperplasia

Summary

Principal Investigator: ROSEBUD ROBERTS
Abstract: DESCRIPTION: (provided by applicant) Benign prostatic hyperplasia (BPH) is the most frequent cause of lower urinary tract symptoms and office visits to urologists among elderly men. Despite this, little is known about the etiology and risk factors for BPH and the only proven risk factors for BPH to date are increasing age and an intact androgen metabolism. Estrogens have also been observed to act synergistically with androgens in the development of BPH. Recent studies suggest that the pathogenesis of BPH is related to a decrease in the serum androgen: estrogen ratio with increasing age. Serum hormone levels, however, have not been consistently associated with BPH risk, possibly because serum levels may not reflect intracellular hormone levels in prostate cells. Since hormone levels within prostate cells may reflect genetic variations, polymorphisms in genes that regulate intracellular androgen and estrogen levels in prostate cells may play an etiologic role in BPH. Several functionally significant polymorphisms have been described for genes that determine androgen and estrogen levels. These polymorphisms may alter the risk of BPH by altering hormone levels or by their effects on androgen and estrogen receptor-mediated events within the prostate. We propose to test the hypothesis that genetic polymorphisms in sex hormone receptors and sex hormone metabolizing enzymes are etiologic risk factors for BPH. In Specific Aim 1 we will test the association between genetic polymorphisms in androgen and estrogen receptor genes and measures of BPH obtained longitudinally in a cohort of men randomly selected from the community. In Specific Aim 2 we will test the association between polymorphisms in genes that encode enzymes involved in androgen and estrogen biosynthesis and activation and measures of BPH in the same cohort. We will evaluate the CYP11A1, CYP17, CYP19, 3Beta hydroxysteroid dehydrogenase, 17BETA hydroxysteroid dehydrogenase types 2,3, 5, and SRD5A2 genes. In SpecificAim 3 we will test the association between polymorphisms in genes that encode enzymes involved in estrogen bioactivation and inactivation and measures of BPH in the same cohort. These genes include CYP1A1, CYP1A2, CYP1B1, catechol 0-methyl transferase, sulfotransferase 1A1, and glutathione S-transferases (M1, P1, and T1). This community-based cohort study should provide insights that should improve our understanding of the genetic control of hormonal mechanisms in the pathogenesis of BPH.
Funding Period: 2002-03-16 - 2006-01-31
more information: NIH RePORT

Top Publications

  1. ncbi Polymorphisms in genes involved in sex hormone metabolism may increase risk of benign prostatic hyperplasia
    Rosebud O Roberts
    Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Prostate 66:392-404. 2006
  2. ncbi Growth factor, cytokine, and vitamin D receptor polymorphisms and risk of benign prostatic hyperplasia in a community-based cohort of men
    Rebecca J Mullan
    Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    Urology 67:300-5. 2006
  3. ncbi Dementia and low testosterone and bioavailable testosterone levels in men: possible increased risk
    Sri Suravarapu
    Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA
    Alzheimer Dis Assoc Disord 20:138-40. 2006
  4. pmc Population-based case-control study of PSA and DRE screening on prostate cancer mortality
    Eric J Bergstralh
    Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Urology 70:936-41. 2007

Scientific Experts

  • ROSEBUD ROBERTS
  • Eric J Bergstralh
  • Steven J Jacobsen
  • Sara A Farmer
  • Michael M Lieber
  • Sri Suravarapu
  • Rebecca J Mullan
  • Jeffrey M Slezak
  • Debra J Jacobson
  • Scott J Hebbring
  • Stephen N Thibodeau
  • David S Knopman
  • Julie M Cunningham

Detail Information

Publications4

  1. ncbi Polymorphisms in genes involved in sex hormone metabolism may increase risk of benign prostatic hyperplasia
    Rosebud O Roberts
    Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Prostate 66:392-404. 2006
    ..This study investigates associations between polymorphisms in genes involved in sex hormone metabolism and measures of benign prostatic hyperplasia (BPH)...
  2. ncbi Growth factor, cytokine, and vitamin D receptor polymorphisms and risk of benign prostatic hyperplasia in a community-based cohort of men
    Rebecca J Mullan
    Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    Urology 67:300-5. 2006
    ..To investigate the associations between benign prostatic hyperplasia (BPH) and polymorphisms in genes that encode growth factors, cytokines, and vitamin D and their receptors...
  3. ncbi Dementia and low testosterone and bioavailable testosterone levels in men: possible increased risk
    Sri Suravarapu
    Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA
    Alzheimer Dis Assoc Disord 20:138-40. 2006
    ..22 (95% CI=0.38, 3.87). These findings do not demonstrate a significant association between T levels and dementia. However, they suggest a need for further investigation of these potential associations...
  4. pmc Population-based case-control study of PSA and DRE screening on prostate cancer mortality
    Eric J Bergstralh
    Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Urology 70:936-41. 2007
    ..In an earlier case-control study, we found that DRE might reduce PCa mortality. The present case-control study assessed the association between PSA and DRE testing and PCa mortality...