A Prospective Study of Diet and Prostate Cancer

我们建议检查四个相互关联的致病途径前列腺癌：维生素D 轴、炎症、性类固醇和胰岛素/胰岛素样生长因子信号传导。我们假设， 前列腺癌的拟议可修改因素（维生素D，钙，牛奶，抗氧化剂，n-3的摄入量） 脂肪酸、多不饱和脂肪、高胰岛素血症饮食、肥胖症、抗炎剂）可能起作用 通过这些途径。更好地了解可改变的风险因素如何与遗传 通过这些机制操作易感性可以帮助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方面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性的分子特征有关， 肿瘤因此，我们将另外检查饮食和激素因素，这些因素被确定为与 前列腺癌的侵袭行为与决定生物学特性的特定分子特征有关 侵袭潜力，如分化和血管生成。此外，我们将研究是否 在诊断后阶段，已确定的饮食和其他可改变的风险因素可影响生存率 在因明显局限于器官的前列腺癌而接受前列腺切除术的男性中。 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， 进展，我们将使用卫生专业人员随访研究（HPFS）的数据，这是一项47，000人的队列研究。 1986年基线时没有癌症的男性。我们预计到2008年将有5,502例前列腺癌新发病例，其中包括 579例死亡病例，1,700多例直肠切除术病例的肿瘤块。暴露数据的来源 在HPFS中有（1）问卷，包括饮食、人体测量、活动、药物使用，（2） 血浆样品和（3）DMA。结局数据将基于（1）病历和病理报告 对初步诊断和生存率的审查，以及（2）与疾病相关的组织块标志物 进展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，可能有助于我们了解可改变的风险因素 前列腺癌的发病率、进展和生存率。我们的最终目标是更好地理解 饮食和其他可变因素，包括广泛使用的药物，如阿司匹林和他汀类药物， 前列腺癌在各个阶段的发生，包括诊断后，并确定易感的男性， 最有可能受益于特定的饮食和生活方式的改变。

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.