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

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.
    

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).
    

Observational model: Case-Only
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Prostate cancer cases diagnosed at the collaborating centers
      
Keywords: Androgens; Serum; Tissue