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广泛的 饮食和饮食相关的生活方式因素影响前列腺癌的风险，并围绕两种机制进行组织：类固醇激素、胰岛素和胰岛素样生长因子刺激细胞生长；以及氧化损伤导致的体细胞突变积累。这项修订提案中的重大修改包括更详细和假设驱动的交叉项目目标，更准确的样本量估计，以及关于肥胖和血糖指数的初步研究的完成。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，我们将检查：(1)影响每个假设机制的饮食因素是否与前列腺癌风险相关，以及(2)非那雄胺对前列腺癌风险的影响是否被饮食和饮食相关因素改变。在与项目4的合作中，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、程度和特征的相关性。在所有其他P01项目的目标中明确了进一步的合作，研究前列腺癌的风险是下列因素共同作用的结果：(A)类固醇激素与肥胖症；(B)肥胖症与胰岛素抵抗；(C)乳制品与IGF；(D)抗氧化剂与炎症；(E)抗氧化剂和氧化应激基因的多态。所有分析的主要终点将是活检检测到的前列腺癌的存在或不存在，这将被描述为完全癌症或低级别和高级别疾病(Gleason评分2-6比7-10)。使用嵌套病例对照设计，我们将有80%的能力检测总前列腺癌的最小优势比为1.29，高级别疾病的最小优势比为1.86，对比饮食暴露的最高和最低四分位数。这项研究将提供大量关于饮食与前列腺癌发病关系的新信息。它还可能有助于确定与饮食有关的特征，这些特征可用于选择最有可能从非那雄胺治疗中受益的人，或用于确定饮食 可作为辅助治疗以增加非那雄胺疗效的修饰或补充。