Intraprostatic Androgenicity in Relation to Circulating Levels of Hormones and Polymorphisms of Hormone-Related Genes: A Methodologic Study

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00342433
Collaborator
(none)
553
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252.4
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Study Details

Study Description

Brief Summary

Although compelling evidence from laboratory studies suggests that androgens play a major role in prostate carcinogenesis, epidemiologic studies in humans (almost exclusively serologic studies) have been unable to confirm the hormonal hypothesis. The major limitation in these serologic studies may stem from difficulty in measuring androgenicity directly at the target site - the prostate. If circulating hormones do not reflect intraprostatic hormone levels or androgenicity, it is not clear how we should interpret results from serum/plasma measurements, and it is unlikely that future serologic studies can clarify the role of hormones in prostate cancer etiology.

This study is a comprehensive methodologic study designed to collect venous blood and prostatic tissue from 650 patients (100 Chinese, 500 American, and 50 Italian) undergoing prostatic surgery (radical prostatectomy, cystoprostatectomy, or transurethral resection of the prostate) in order to correlate prostate tissue with serum hormone levels, and with polymorphisms of hormone-related genes (including the androgen receptor and SRD5A2, the gene encoding 5-alpha-reductase Type II), and to examine characteristics (such as age, smoking, body size) that might affect serum-tissue correlation. We plan to study the following hormones: testosterone, dihydrotestosterone, androstenedione, androstandediol glucuronide, estradiol, estrone, and estrone sulfate. Levels of androgen receptor and its associated protein in prostatic tissue will also be measured to provide a better estimate of total intraprostatic androgenicity. We also plan to collect saliva from 100 of these cases in the Washington, D.C. area and 100 of these cases in China, to assess whether this non-invasive tissue collection method is valid for hormone measurements. Finally, urine collection from 100 of these Chinese men is planned for study of androgen metabolites.

Additionally, we plan to include 200 Chinese subjects for blood collection without tumor tissue for gene polymorphism studies, bringing the total number of subjects enrolled to 850.

For the 650 subjects providing prostate tissue, 30-ml of fasting blood will be collected for hormone and polymorphism analyses, and tissue will be collected at surgery. A 15-minute interview will be conducted to elicit information on demographic characeristics, tobacco and alcohol use, body size, and medical history.

The proposed methodologic study will be the first of its kind to investigate androgenicity in target tissues directly, and the correlation of target tissue androgenicity with circulating levels of hormones and polymorphisms of hormone-related genes in a well-designed epidemiologic study. This study will provide critical information to guide future analytic studies on hormones and prostate cancer.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    Although androgens (male hormones) have been the central hypothesis in prostate cancer etiology for decades, epidemiologic studies in humans have not been able to confirm this hormonal hypothesis. Most of the studies used sere (blood) to examine the relationships of circulating hormones with subsequent prostate cancer risk. However, it is possible that circulating levels of hormones may not reflect intraprostatic and androgenic activity accurately.

    To gain further insights and to provide directions for future epidemiologic studies, the National Cancer Institute (NCI) is conducting a comprehensive methodological study called Intraprostatic androgenicity in relation to circulating levels of hormone and polymorphisms of hormone-related genes: a methodologic study. The specific aims of this study are:

    • to correlate circulating levels of androgens and estrogens with tissue levels (including testosterone, DHT, DHT sulfate, androstenedione, androstanediol glucuronide, estradiol, estrone, and estrone sulfate);

    • to determine whether the serum-tissue correlation is mediated by age, race, and selected epidemiologic factors, such as smoking and body size;

    • to determine whether tissue hormone levels correlate with polymorphisms of certain hormone-related genes, including androgen receptor (AR) and SRD5A2; and

    • to correlate circulating levels of hormones with intraprostatic androgenicity, as defined by the combined levels of tissue hormones, androgen receptor, and its associated protein (ARA70).

    Study Design

    Study Type:
    Observational
    Actual Enrollment :
    553 participants
    Observational Model:
    Case-Only
    Time Perspective:
    Cross-Sectional
    Official Title:
    Intraprostatic Androgenicity in Relation to Circulating Levels of Hormones and Polymorphisms of Hormone-Related Genes: A Methodologic Study
    Actual Study Start Date :
    May 5, 1999
    Actual Primary Completion Date :
    May 15, 2020
    Actual Study Completion Date :
    May 15, 2020

    Arms and Interventions

    Arm Intervention/Treatment
    Localized Prostate Cancer cases

    Cases enrolled between Jan 2000 and Apr 2004 at five locations. Study subject eligibility: Age >=18; scheduled for radical prostatectomy; and newly diagnosed with localized prostate cancer.

    Outcome Measures

    Primary Outcome Measures

    1. Intraprostatic hormone concentrations [Cross-sectional]

      comparisons between circulating and intraprostatic hormones

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 100 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    • INCLUSION CRITERIA:

    Subjects must be over age 18.

    Subjects must have a newly diagnosed prostate disease or condition.

    Subjects must not currently take hormones.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of California, San Francisco San Francisco California United States 94143
    2 Washington Hospital Center Washington District of Columbia United States 20010
    3 GW University Medical Center GW Hospital Center Washington District of Columbia United States 20037
    4 Doctors Community Hospital Lanham Maryland United States
    5 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States
    6 Fairfax Hospital Falls Church Virginia United States 22046
    7 Shanghai Cancer Institute Shanghai China

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Michael B Cook, M.D., National Cancer Institute (NCI)

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00342433
    Other Study ID Numbers:
    • 999999025
    • OH99-C-N025
    First Posted:
    Jun 21, 2006
    Last Update Posted:
    May 20, 2020
    Last Verified:
    May 1, 2020
    Keywords provided by National Cancer Institute (NCI)

    Study Results

    No Results Posted as of May 20, 2020