Biology of the Prostate Cancer Prevention Trial (PCPT)

前列腺癌预防试验 (PCPT) 的生物学

• 批准号: 7059466
• 负责人: SCOTT M LIPPMAN
• 金额: $ 305.71万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7059466
• 关键词: cancer prevention; chemoprevention; human data; meta analysis; prostate neoplasms

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.

前列腺癌是最常见的非皮肤癌，是美国男性癌症死亡的第二大原因，并且发病率正在上升。有效的预防需要更好地了解前列腺癌的病因，这是本P01历史前列腺癌预防试验（PCPT）生物学研究的主要目标。在18882名男性中进行的一项随机对照试验中，PCPT发现非那雄胺降低了24.8%的前列腺癌总体风险，并明显增加了高级别疾病的风险（新英格兰医学杂志[NEJM]， 2003年7月）。前列腺癌是一种雄激素依赖性疾病，非那雄胺抑制5a-还原酶，从而阻断睾酮（通过5a-还原酶）向双氢睾酮（最活跃的前列腺雄激素）的转化。提出的5个高度相互作用的P01研究是：项目1，雄激素代谢；项目二：饮食及饮食相关因素；项目3，胰岛素样