Prostate cancer is the most frequent non-skin cancer, the second leading cause of cancer death in U.S. men, and is increasing in incidence. Effective prevention requires a better understanding of the etiology of prostate cancer, a major goal of this P01's biological studies of the historical Prostate Cancer Prevention Trial (PCPT). A randomized, controlled trial of finasteride in 18,882 men, the PCPT found a 24.8% decrease in overall prostate cancer risk and an apparently increased risk of high-grade disease (New England Journal of Medicine [NEJM], July 2003). Prostate cancer is an androgen-dependent disease, and finasteride inhibits 5a-reductase, thus blocking the conversion of testosterone (by 5a-reductase) to dihydrotestosterone, the most active prostate androgen. The five proposed highly interactive P01 studies of the PCPT are: Project 1, Androgen Metabolism;Project 2, Diet and Diet-Related Factors;Project 3, Insulin-like Growth Factor Axis and Insulin Resistance;Project 4, Genotypic and Phenotypic Studies of Inflammation;and Project 5, Oxidative Damage and DNA Repair. These projects will use nested case (n=1800)-control (n=1800) designs to develop the P01 theme, which is the genetic, metabolic and environmental factors associated with the risk of prostate cancer overall or high-grade disease and the effects of these factors on finasteride preventive efficacy. The mechanisms underlying these risk-factor associations also will be assessed. Major elements of the P01 theme are the study (1) of genetic polymorphisms to identify molecular prostate cancer risk factors and determine pharmacogenetic profiles and (2) of somatic mutations to discover the mechanisms underlying increased high-grade prostate cancer risk associated with finasteride. The P01 provides each project access to the invaluable repository of PCPT biospecimens and data. Each project is closely linked by interactive specific aims and planned collaborations with the other 4 projects and 3 cores. Unique P01 strengths include its biopsy-confirmed control group, the value of which is underscored by PCPT data indicating a substantial prevalence of cancer and high-grade disease in men with """"""""normal"""""""" prostate-specific antigen and digital rectal exam (NEJM, May 2004), and standard centralized histological classifications. With fully clarified interactions and a large amount of highly relevant new preliminary data, this resubmitted P01 promises to develop comprehensive prostate cancer risk models important to the future study and prevention of prostate cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
7P01CA108964-06
Application #
7924437
Study Section
Subcommittee G - Education (NCI)
Program Officer
Parnes, Howard L
Project Start
2005-05-01
Project End
2014-04-30
Budget Start
2010-03-24
Budget End
2014-04-30
Support Year
6
Fiscal Year
2009
Total Cost
$2,227,911
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Urology
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Tang, Li; Platek, Mary E; Yao, Song et al. (2018) Associations between polymorphisms in genes related to estrogen metabolism and function and prostate cancer risk: results from the Prostate Cancer Prevention Trial. Carcinogenesis 39:125-133
Winchester, Danyelle A; Till, Cathee; Goodman, Phyllis J et al. (2017) Association between variants in genes involved in the immune response and prostate cancer risk in men randomized to the finasteride arm in the Prostate Cancer Prevention Trial. Prostate 77:908-919
Miles, Fayth L; Goodman, Phyllis J; Tangen, Catherine et al. (2017) Interactions of the Insulin-Like Growth Factor Axis and Vitamin D in Prostate Cancer Risk in the Prostate Cancer Prevention Trial. Nutrients 9:
Chen, Haitao; Liu, Xu; Brendler, Charles B et al. (2016) Adding genetic risk score to family history identifies twice as many high-risk men for prostate cancer: Results from the prostate cancer prevention trial. Prostate 76:1120-9
Murtola, Teemu J; Gurel, Bora; Umbehr, Martin et al. (2016) Inflammation in Benign Prostate Tissue and Prostate Cancer in the Finasteride Arm of the Prostate Cancer Prevention Trial. Cancer Epidemiol Biomarkers Prev 25:463-9
Price, Douglas K; Chau, Cindy H; Till, Cathee et al. (2016) Association of androgen metabolism gene polymorphisms with prostate cancer risk and androgen concentrations: Results from the Prostate Cancer Prevention Trial. Cancer 122:2332-40
(2016) Correction: Durable Antibody Responses Following One Dose of the Bivalent Human Papillomavirus L1 Virus-Like Particle Vaccine in the Costa Rica Vaccine Trial. Cancer Prev Res (Phila) 9:116-7
Patel, Darshan P; Schenk, Jeannette M; Darke, Amy et al. (2016) Non-steroidal anti-inflammatory drug (NSAID) use is not associated with erectile dysfunction risk: results from the Prostate Cancer Prevention Trial. BJU Int 117:500-6
Travis, Ruth C; Appleby, Paul N; Martin, Richard M et al. (2016) A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk. Cancer Res 76:2288-2300
Winchester, Danyelle A; Gurel, Bora; Till, Cathee et al. (2016) Key genes involved in the immune response are generally not associated with intraprostatic inflammation in men without a prostate cancer diagnosis: Results from the prostate cancer prevention trial. Prostate 76:565-74

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