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

Prostate Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00342433
• Other study ID #: 999999025
• Secondary ID: OH99-C-N025
• Status: Completed
• Start date: May 5, 1999
• Est. completion date: May 15, 2020

Study information

• Verified date: May 2020
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 553
• Est. completion date: May 15, 2020
• Est. primary completion date: May 15, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 100 Years

Eligibility

• INCLUSION CRITERIA:

Subjects must be over age 18.

Subjects must have a newly diagnosed prostate disease or condition.

Subjects must not currently take hormones.

Related Conditions & MeSH terms

• Prostate

Locations

Country	Name	City	State
China	Shanghai Cancer Institute	Shanghai
United States	Fairfax Hospital	Falls Church	Virginia
United States	Doctors Community Hospital	Lanham	Maryland
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	University of California, San Francisco	San Francisco	California
United States	GW University Medical Center GW Hospital Center	Washington	District of Columbia
United States	Washington Hospital Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  China, 

References & Publications (3)

Hsing AW. Hormones and prostate cancer: where do we go from here? J Natl Cancer Inst. 1996 Aug 21;88(16):1093-5. — View Citation

Montie JE, Pienta KJ. Review of the role of androgenic hormones in the epidemiology of benign prostatic hyperplasia and prostate cancer. Urology. 1994 Jun;43(6):892-9. Review. — View Citation

Vatten LJ, Ursin G, Ross RK, Stanczyk FZ, Lobo RA, Harvei S, Jellum E. Androgens in serum and the risk of prostate cancer: a nested case-control study from the Janus serum bank in Norway. Cancer Epidemiol Biomarkers Prev. 1997 Nov;6(11):967-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intraprostatic hormone concentrations	comparisons between circulating and intraprostatic hormones	Cross-sectional