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

Status:	Completed
Conditions:	Prostate Cancer, Cancer
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	18 - 100
Updated:	12/16/2018
Start Date:	May 5, 1999

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.

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).

- INCLUSION CRITERIA:

Subjects must be over age 18.

Subjects must have a newly diagnosed prostate disease or condition.

Subjects must not currently take hormones.

We found this trial at

sites

Fairfax Hospital

Falls Church, Virginia 22046

from

Falls Church, VA