Diet and Diet-Related Factors in the PCPT

PCPT 中的饮食和饮食相关因素

• 批准号: 7102927
• 负责人: SCOTT M LIPPMAN
• 金额: $ 25.75万
• 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: 2005-04-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7102927
• 关键词: antioxidants; biopsy; cancer prevention; cancer risk; cell transformation; clinical research; clinical trials; dietary constituent; fatty acids; finasteride; gene mutation; hormone metabolism; human data; lifestyle; longitudinal human study; neoplasm /cancer epidemiology; nutrient drug interaction; nutrient interaction; nutrition related tag; oxidative stress; phospholipids; prostate neoplasms; steroid hormone

DESCRIPTION (provided by applicant): This revised study proposes to examine whether a broad range of dietary and diet-related lifestyle factors affect prostate cancer risk, and is organized around two mechanisms that could mediate effects of diet on prostate carcinogenesis: stimulation of cell growth by steroid hormones, insulin and insulin-like growth factors; and accumulation of somatic mutations caused by oxidative damage. Significant modifications in this revised proposal include more detailed and hypothesis-driven Cross-Project Aims, more accurate estimates of sample sizes, and completion of pilot studies on obesity and glycemic index. Using comprehensive data from the PCPT on diet-related exposures, including serum, anthropometric measures and dietary assessments, we will examine: (1) whether dietary factors that affect each postulated mechanism are associated with risk of prostate cancer and (2) whether the effects of finasteride on prostate cancer risk are modified by diet and diet-related factors. In collaboration with Project 4, we propose to examine associations of dietary and phospholipid fatty acids with the extent, degree and characteristics of inflammation and atrophy in prostate tissue biopsies. Further collaborations are specified in the aims of all other P01 projects, examining risk of prostate cancer as a function of joint associations between: (a) steroid hormones and obesity; (b) obesity and insulin resistance; (c) dairy products and IGFs; (d) antioxidants and inflammation; and (e) antioxidants and polymorphisms in oxidative stress genes. The primary endpoint for all analyses will be the presence or absence of biopsy-detected prostate cancer, which will be characterized either as total cancer or as low- and high-grade disease {Gleason score 2-6 vs. 7-10). Using a nested case-control design, we will have 80% power to detect a minimum odds ratio for total prostate cancer of 1.29 and 1.6 for high-grade disease of 1.86, contrasting highest to lowest quartiles of dietary exposures. This study will yield substantial new information about the relationships of diet with the development of prostate cancer. It may also help to identify diet-related characteristics that could be used to select persons most likely to benefit from finasteride treatment, or to identify dietary modifications or supplements that could be used as adjunct treatment to increase finasteride efficacy.

描述（由申请人提供）：这项修订后的研究建议检查是否广泛 一系列饮食和饮食相关的生活方式因素影响前列腺癌的风险，并围绕着两种机制，可以调解饮食对前列腺癌发生的影响：类固醇激素，胰岛素和胰岛素样生长因子刺激细胞生长;和氧化损伤引起的体细胞突变的积累。本修订提案中的重大修改包括更详细和假设驱动的跨项目目标，更准确的样本量估计，以及完成肥胖和血糖指数的试点研究。利用PCPT关于饮食相关暴露的综合数据，包括血清、人体测量和饮食评估，我们将研究：（1）影响每种假设机制的饮食因素是否与前列腺癌风险相关;（2）饮食和饮食相关因素是否改变了芬那肽对前列腺癌风险的影响。与项目4合作，我们建议检查饮食和磷脂脂肪酸与前列腺组织活检中炎症和萎缩的程度，程度和特征的关系。所有其他P01项目的目标都规定了进一步的合作，研究前列腺癌的风险作为以下因素之间联合关联的函数：（a）类固醇激素和肥胖;（B）肥胖和胰岛素抵抗;（c）乳制品和胰岛素样生长因子;（d）抗氧化剂和炎症;（e）抗氧化剂和氧化应激基因多态性。所有分析的主要终点将是活检检测的前列腺癌的存在或不存在，其将被表征为总癌症或低级别和高级别疾病（格里森评分2-6对比7-10）。使用巢式病例对照设计，我们将有80%的把握度检测总前列腺癌的最小比值比为1.29，高级别疾病的最小比值比为1.61，将饮食暴露的最高四分位数与最低四分位数进行对比。这项研究将产生大量关于饮食与前列腺癌发展关系的新信息。它也可能有助于确定饮食相关的特征，可用于选择最有可能从芬那肽治疗中获益的人，或确定饮食相关的特征。 可用作辅助治疗以增加芬那肽功效的修饰或补充剂。