A Prospective Study of Diet and Prostate Cancer

饮食与前列腺癌的前瞻性研究

• 批准号: 7191213
• 负责人: EDWARD GIOVANNUCCI
• 金额: $ 50.75万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7191213
• 关键词: Accounting; Age; Aggressive behavior; Alleles; Anti-Inflammatory Agents; Antioxidants; Aspirin; Atrophic; C-Peptide; CYP2C9 gene; Calcium; Calcium Milk; Cancerous; Cessation of life; Characteristics; Chemoprevention; Chronic; Chronic Inflammatory Infiltrate; Complex; Data; Diagnosis; Diagnostic; Diet; Dietary Factors; Disease Progression; Dose; Down-Regulation; Ejaculation; Elderly; Estradiol; Etiology; Exercise; Exhibits; Fatty acid glycerol esters; Fatty-acid synthase; Fishes; Follow-Up Studies; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Variation; Goals; Gonadal Steroid Hormones; Grant; Health Professional; Heterogeneity; Hormonal; Hormones; Hyperinsulinism; Immune response; Incidence; Inflammation; Inflammatory; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Intake; Lesion; Life Style; Localized; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Mediating; Medical Records; Metabolic syndrome; Metabolism; Milk; Mixed Function Oxygenases; Modeling; Molecular; Multivariate Analysis; Non-Steroidal Anti-Inflammatory Agents; Obesity; Omega-3 Fatty Acids; Organ; Outcome; Pathology Report; Pathway interactions; Pharmaceutical Preparations; Physical activity; Plasma; Polyunsaturated Fatty Acids; Prevention strategy; Prospective Studies; Prostate; Prostatectomy; Prostatic; Protein Overexpression; Questionnaires; Range; Research Personnel; Risk; Risk Factors; Sampling; Signal Transduction; Somatomedins; Source; Staging; Testosterone; Tissues; Trichomonas vaginalis; Variant; Vitamin D; Vitamin D2; Vitamin D3 Receptor; Vitamin E; adiponectin; angiogenesis; base; carcinogenesis; cohort; driving force; energy balance; high risk men; improved; indexing; insulin secretion; lycopene; men; modifiable risk; nutrition; outcome forecast; prevent; programs; prostatitis; receptor expression; response; tumor

We propose to examine four inter-related pathogenic pathways for prostate carcinogenesis: the vitamin D axis, inflammation, sex steroids, and insulin/insulin-like growth factor signaling. We hypothesize that many of the proposed modifiable factors for prostate cancer (intakes of vitamin D, calcium, milk, antioxidants, n-3 fatty acids, polyunsaturated fat, hyperinsulinemic diets, obesity, anti-inflammatory agents) may operate through these pathways. A better understanding of how modifiable risk factors in conjunction with genetic susceptibility operate through these mechanisms can help optimize preventive strategies for prostate cancer. In addition, prostate cancers exhibit a profound range of heterogeneity in biologic potential for progression among tumors. We hypothesize that this heterogeneity is related to acquired molecular characteristics in the tumor. Thus, we will additionally examine dietary and hormonal factors that are identified to be related to aggressive behavior in prostate cancer in relation to specific molecular characteristics that determine biologic aggressive potential, such as differentiation and angiogenesis. In addition, we will examine whether identified dietary and other modifiable risk factors can, in the post-diagnostic period, influence survival among men treated with prostatectomy for apparently organ-confined prostate cancer. To accomplish our aims to dietary, hormonal, and genetic factors related to prostate cancer incidence and progression, we will use data in the Health Professionals Follow-up Study (HPFS), a cohort of the 47,000 men free of cancer at baseline in 1986. We project 5,502 new cases of prostate cancer by 2008, including 579 fatal cases, with tumor blocks from over 1,700 prostatectomy cases. The sources of the exposure data in the HPFS are (1) questionnaire, including diet, anthropometric measures, activity, medication use, (2) plasma samples, and (3) DMA. The outcome data will be based on (1) medical record and pathology report review for initial diagnosis and survival, and (2) tissue block markers that correlated with disease progression. We will use multivariate analysis to control for confounding factors. This project is likely to yield important new findings that may help our understanding of modifiable risk factors for prostate cancer incidence, progression, and survival. Our ultimate goal is to better understand how dietary and other modifiable factors, including widely used medications such as aspirin and statins, influence prostate carcinogenesis at various stages, including after diagnosis, and to identify the susceptible men who would be most likely to benefit from specific dietary and lifestyle changes.

我们建议研究前列腺癌发生的四个相互关联的致病途径：维生素D 轴、炎症、性激素和胰岛素/胰岛素样生长因子信号。我们假设有很多人 前列腺癌的拟议可修改因素(摄入维生素D、钙、牛奶、抗氧化剂、n-3 脂肪酸、多不饱和脂肪、高胰岛素饮食、肥胖、抗炎剂)可能起作用 通过这些小路。更好地理解可改变的风险因素如何与基因 易感性通过这些机制发挥作用，有助于优化前列腺癌的预防策略。 此外，前列腺癌在生物学进展潜力上表现出深刻的异质性。 在肿瘤中。我们假设这种异质性与获得的分子特征有关。 肿瘤。因此，我们将额外检查被确定与以下因素有关的饮食和激素因素 前列腺癌侵袭性行为与决定生物学行为的特定分子特征的关系 侵袭性潜能，如分化和血管生成。此外，我们还将研究是否 在诊断后阶段，已确定的饮食和其他可改变的危险因素可能会影响存活率。 在接受前列腺切除术的男性中，他们显然是器官受限的前列腺癌患者。 为了实现我们的目标，饮食，激素和遗传因素与前列腺癌的发病率和 进展，我们将使用卫生专业人员后续研究(HPFS)中的数据，这是一个由47,000人组成的队列 1986年，男性在基线上没有癌症。我们预计到2008年有5,502例前列腺癌新病例，包括 579例死亡病例，1700多例前列腺切除术中的肿瘤块。暴露数据的来源 在HPFS中有(1)问卷，包括饮食、人体测量、活动、用药情况，(2) 血浆样本，以及(3)DMA。结果数据将基于(1)医疗记录和病理报告 (2)与疾病相关的组织块标志物 进步。我们将使用多变量分析来控制混杂因素。 这个项目可能会产生重要的新发现，可能有助于我们理解可改变的风险因素 前列腺癌的发病率、进展和存活率。我们的最终目标是更好地理解 饮食和其他可改变的因素，包括广泛使用的阿司匹林和他汀类药物，会影响 前列腺癌发生的不同阶段，包括确诊后，并找出易感人群 最有可能从具体的饮食和生活方式的改变中受益。