Cohort Study of Risks for Benign Prostatic Hyperplasia

Summary

Principal Investigator: Alan Kristal
Affiliation: Fred Hutchinson Cancer Research Center
Country: USA
Abstract: The overall goal of this application is to understand relationships among hormonal, genetic and behavioral risk factors for symptomatic benign prostatic hyperplasia (BPH). BPH symptoms affect well over half of American men over age 50, with substantial effects on quality of life and medical care cost of over 4 billion dollars annually. This study will assess whether the risk of symptomatic BPH is associated with (1) serum concentrations of steroid hormones and insulin-like growth factors known to affect prostate growth; (2) polymorphisms in genes that affect hormone and growth factor metabolism or activity; and (3) diet and other lifestyle factors that affect steroid hormones and insulin-like growth factor concentration or activity. Data are from the Prostate Cancer Prevention Trial (PCPT), a double blinded, placebo-controlled, randomized trial of the drug finasteride (Proscar) for the primary prevention of prostate cancer. Analyses will be restricted to the approximate 5,000 men in the placebo control group with no medical history or symptoms of BPH at baseline. The primary endpoint, incidence of symptomatic BPH, is based on careful and standardized assessments of lower urinary tract symptoms and treatment for prostate-related disease collected at baseline and annually for 7 years. Steroid hormones, insulin-like growth factor 1 and insulin-like growth factor binding protein 3 will be measured from plasma banked at baseline, and genetic characteristics will be assessed using banked lymphocytes. Diet and other behavioral risk factors were assessed by both interviewer- and self-administered questionnaires. A nested case-control design, with 700 cases and 700 controls, will be used to address hypotheses related to serum measures and genetic polymorphisms. A cohort study using all 5,000 men will be used to examine hypotheses related to diet and other behavioral risk factors. The nested case-control studies are powered to detect odds ratios of 1.5 and the cohort studies are powered to detect hazard ratios of 1.35, comparing highest to lowest quartiles of exposures, with type I error = 0.05 and type II error = 0.20. This study is highly cost-effective, as all data and samples have been collected, and funds are requested for laboratory analyses of serum and genetic polymorphisms, data preparation, statistical analyses and manuscript preparation. Results from this study will enhance our understanding of the etiology of symptomatic BPH and could potentially be used to develop new strategies for prevention and control of this very common disease.
Funding Period: 2003-07-01 - 2007-06-30
more information: NIH RePORT

Top Publications

  1. ncbi Race/ethnicity, obesity, health related behaviors and the risk of symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial
    Alan R Kristal
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    J Urol 177:1395-400; quiz 1591. 2007
  2. pmc Plasma vitamin d and prostate cancer risk: results from the selenium and vitamin e cancer prevention trial
    Alan R Kristal
    Cancer Prevention Program Departments of Epidemiology and
    Cancer Epidemiol Biomarkers Prev 23:1494-504. 2014
  3. pmc Should modest elevations in prostate-specific antigen, International Prostate Symptom Score, or their rates of increase over time be used as surrogate measures of incident benign prostatic hyperplasia?
    Jeannette M Schenk
    Fred Hutchinson Cancer Research Center, Cancer Prevention Program, Seattle, WA 98109 1024, USA
    Am J Epidemiol 178:741-51. 2013
  4. pmc Associations of serum sex steroid hormone and 5α-androstane-3α,17β-diol glucuronide concentrations with prostate cancer risk among men treated with finasteride
    Alan R Kristal
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Cancer Epidemiol Biomarkers Prev 21:1823-32. 2012
  5. pmc Indications for and use of nonsteroidal antiinflammatory drugs and the risk of incident, symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial
    Jeannette M Schenk
    Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 1024, USA
    Am J Epidemiol 176:156-63. 2012
  6. pmc Association of symptomatic benign prostatic hyperplasia and prostate cancer: results from the prostate cancer prevention trial
    Jeannette M Schenk
    Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 1024, USA
    Am J Epidemiol 173:1419-28. 2011
  7. pmc Biomarkers of systemic inflammation and risk of incident, symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial
    Jeannette M Schenk
    Schenk, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 1024, USA
    Am J Epidemiol 171:571-82. 2010
  8. pmc Serum adiponectin, C-peptide and leptin and risk of symptomatic benign prostatic hyperplasia: results from the Prostate Cancer Prevention Trial
    Jeannette M Schenk
    Fred Hutchinson Cancer Research Center, Cancer Prevention Program, Seattle, Washington 98109 1024, USA
    Prostate 69:1303-11. 2009
  9. pmc Serum steroid and sex hormone-binding globulin concentrations and the risk of incident benign prostatic hyperplasia: results from the prostate cancer prevention trial
    Alan R Kristal
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4 B402, PO Box 19024, Seattle, WA 98109 1024, USA
    Am J Epidemiol 168:1416-24. 2008
  10. pmc Insulin-like growth factor-I, insulin-like growth factor binding protein-3 and risk of benign prostate hyperplasia in the prostate cancer prevention trial
    Marian L Neuhouser
    Cancer Prevention Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 1024, USA
    Prostate 68:1477-86. 2008

Detail Information

Publications12

  1. ncbi Race/ethnicity, obesity, health related behaviors and the risk of symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial
    Alan R Kristal
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    J Urol 177:1395-400; quiz 1591. 2007
    ..We examined risk factors for incident symptomatic benign prostate hyperplasia in 5,667 Prostate Cancer Prevention Trial placebo arm participants who were free of benign prostatic hyperplasia at baseline...
  2. pmc Plasma vitamin d and prostate cancer risk: results from the selenium and vitamin e cancer prevention trial
    Alan R Kristal
    Cancer Prevention Program Departments of Epidemiology and
    Cancer Epidemiol Biomarkers Prev 23:1494-504. 2014
    ..In vitro, animal, and ecological studies suggest that inadequate vitamin D intake could increase prostate cancer risk, but results of biomarker-based longitudinal studies are inconsistent...
  3. pmc Should modest elevations in prostate-specific antigen, International Prostate Symptom Score, or their rates of increase over time be used as surrogate measures of incident benign prostatic hyperplasia?
    Jeannette M Schenk
    Fred Hutchinson Cancer Research Center, Cancer Prevention Program, Seattle, WA 98109 1024, USA
    Am J Epidemiol 178:741-51. 2013
    ..61, 0.65); however there were no cut points at which sensitivity and specificity were both above 75%. We concluded that moderate elevations in PSA, IPSS, or their rates of change should not be used as surrogate measures of incident BPH. ..
  4. pmc Associations of serum sex steroid hormone and 5α-androstane-3α,17β-diol glucuronide concentrations with prostate cancer risk among men treated with finasteride
    Alan R Kristal
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Cancer Epidemiol Biomarkers Prev 21:1823-32. 2012
    ..It also modestly increases serum testosterone (T), estrone (E(1)), and estradiol (E(2)). In this altered hormonal milieu, it is unknown whether serum concentrations of these hormones are associated with prostate cancer risk...
  5. pmc Indications for and use of nonsteroidal antiinflammatory drugs and the risk of incident, symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial
    Jeannette M Schenk
    Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 1024, USA
    Am J Epidemiol 176:156-63. 2012
    ..06 (95% CI: 0.82, 1.38). The modest associations of NSAID use with BPH risk in this cohort were probably due to confounding by indication, and NSAID use was not associated with BPH risk...
  6. pmc Association of symptomatic benign prostatic hyperplasia and prostate cancer: results from the prostate cancer prevention trial
    Jeannette M Schenk
    Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 1024, USA
    Am J Epidemiol 173:1419-28. 2011
    ..This study provides the strongest evidence to date that BPH does not increase the risk of prostate cancer...
  7. pmc Biomarkers of systemic inflammation and risk of incident, symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial
    Jeannette M Schenk
    Schenk, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 1024, USA
    Am J Epidemiol 171:571-82. 2010
    ..82; interleukin 6: OR = 1.79, 95% CI: 1.32, 2.42); these associations were only in men aged <65 years. Results suggest that systemic inflammation or lower levels of soluble receptors that bind inflammatory cytokines increase BPH risk...
  8. pmc Serum adiponectin, C-peptide and leptin and risk of symptomatic benign prostatic hyperplasia: results from the Prostate Cancer Prevention Trial
    Jeannette M Schenk
    Fred Hutchinson Cancer Research Center, Cancer Prevention Program, Seattle, Washington 98109 1024, USA
    Prostate 69:1303-11. 2009
    ..We examined whether adiponectin, leptin, and C-peptide were associated with incident, symptomatic BPH and whether these factors mediate the relationship between obesity and BPH risk...
  9. pmc Serum steroid and sex hormone-binding globulin concentrations and the risk of incident benign prostatic hyperplasia: results from the prostate cancer prevention trial
    Alan R Kristal
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4 B402, PO Box 19024, Seattle, WA 98109 1024, USA
    Am J Epidemiol 168:1416-24. 2008
    ..Genetic or environmental factors that affect the activity of 5-alpha-reductase may be important in the development of symptomatic BPH...
  10. pmc Insulin-like growth factor-I, insulin-like growth factor binding protein-3 and risk of benign prostate hyperplasia in the prostate cancer prevention trial
    Marian L Neuhouser
    Cancer Prevention Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 1024, USA
    Prostate 68:1477-86. 2008
    ....
  11. doi Dietary patterns, supplement use, and the risk of symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial
    Alan R Kristal
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 1024, USA
    Am J Epidemiol 167:925-34. 2008
    ..A diet low in fat and red meat and high in protein and vegetables, as well as regular alcohol consumption, may reduce the risk of symptomatic BPH...
  12. ncbi Associations of demographic and lifestyle characteristics with prostate-specific antigen (PSA) concentration and rate of PSA increase
    Alan R Kristal
    Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 1024, USA
    Cancer 106:320-8. 2006
    ..The objective of this study was to examine whether demographic and lifestyle characteristics are associated with prostate-specific antigen (PSA) levels and the rate of PSA increase (PSA velocity)...