Incidence and mortality rates for prostate cancer among African-American men in Detroit are among the highest in the world. The extraordinary impact of this disease on our community has led to the development of several large NIH funded research studies of prostate cancer. Two of these studies focus on the etiology of prostate cancer. One, a study of the frequency and extent of prostatic intraepithelial neoplasia and latent prostate cancer at autopsy of sudden death victims, documents frequencies of the earliest microscopic precursors of prostate cancer. The second, a population-based case-control study, characterizes determinants of clinical disease. The autopsy study includes over 600 subjects cases and the case-control study over 700 cases and an equivalent number of controls. Both include a high proportion of African-American men. Although extensive, these studies do not address the role of genetic susceptibility in the etiology of prostate cancer. Recent studies reporting associations between genetic polymorphisms and prostate cancer risk provide important opportunities for determining the etiology of prostate cancer using the data and tissue resources from our ongoing studies. The polymorphisms include factors governing the biological effects of androgens, (polymorphisms in the androgen receptor gene itself and enzymes determining the synthesis and degradation of active forms of testosterone) and the biological effectiveness of vitamin D (polymorphisms in the receptor). Analysis of specimens from our ongoing studies will allow investigations of the impact of these polymorphisms on both the earliest detectable phase of prostate cancer in the autopsy study and its progression to clinical disease in the case-control study. Our analysis will emphasize comparisons of findings for African-American and Caucasian males from the same community. This project will provide a valuable opportunity to define the role of the individual effects and the interplay of androgens, vitamin D, and race in the etiology of prostate cancer, and to distinguish their effects on its preclinical initiation and progression to clinical disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA084989-02
Application #
6377558
Study Section
Special Emphasis Panel (ZRG1-EDC-2 (01))
Program Officer
Silkensen, Shannon M
Project Start
2000-08-23
Project End
2004-07-31
Budget Start
2001-08-01
Budget End
2002-07-31
Support Year
2
Fiscal Year
2001
Total Cost
$331,012
Indirect Cost
Name
Wayne State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
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