Etiologic Studies of Prostate Cancer

目前的项目重点领域包括：1)维生素D、E和A；2)遗传决定因素，包括通过GWAS和基于途径的候选因素；3)胰岛素、甲状腺激素、雄激素；4)代谢组学分析。该项目调查了一系列营养和相关因素，重点关注维生素E、D和其他微量营养素、能量平衡、胰岛素和生长因子、激素和遗传因素在几个项目中的作用，包括α -生育酚、β -胡萝卜素癌症预防（ATBC）研究、NCI乳腺癌和前列腺癌队列联盟（BPC3）、硒和维生素E癌症预防试验（SELECT）、美国国立卫生研究院-美国退休人员协会（AARP）研究、前列腺癌、肺癌、结直肠癌和卵巢癌筛查（PLCO）试验，以及前列腺癌预防试验（PCPT）项目的生物学。其中一些涉及发现前列腺癌遗传决定因素的联合方法，这些方法有助于我们了解这种恶性肿瘤和一些假设的生物学途径。这些基因正在作为候选基因进行评估，并通过GWAS进行评估，包括循环营养表型（一个新的发现领域，正在为前列腺和其他癌症提供有用的线索）。循环胰岛素样生长因子和胰岛素已被研究，发现有很强的病因关联，而较高的雄激素水平被证明不是一个重要的危险因素。ATBC研究中新的前列腺病例对照数据显示，25oh -维生素D与前列腺癌有很强的正相关性，维生素D代谢和信号基因以及测试基因-营养相互作用正在研究中。

Current project emphasis areas include: 1) vitamin D, E and A; 2) genetic determinants, including through GWAS and pathway-based candidates; 3) insulin, thyroid hormones, and androgens; 4) metabolomics profiling.The project investigates a range of nutritional and related factors, concentrating on the role of vitamins E, D and other micronutrients, energy balance, insulin and growth factors, hormones, and genetic factors within several projects, including the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, the NCI Breast and Prostate Cancer Cohort Consortium (BPC3), the Selenium and Vitamin E Cancer Prevention Trial (SELECT), the NIH-American Association of Retired Persons (AARP) Study, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening (PLCO) Trial, and the Biology of the Prostate Cancer Prevention Trial (PCPT) Project. Some of these involve consortium approaches to discovering genetic determinants of prostate cancer that have contributed to our knowledge of this malignancy and some hypothesized biological pathways. The genes are being evaluated as candidates and through GWAS, including of circulating nutrient phenotypes (a new area of discovery that is providing useful leads with respect to prostate and other cancers). Circulating insulin-like growth factors and insulin have been studied, with strong etiologic associations found, whereas higher androgen status was shown to not be an important risk factor. New prostate case-control data in the ATBC Study showed a strong positive 25OH-vitamin D-prostate cancer association, and vitamin D metabolizing and signaling genes and testing gene-nutrient interactions are being examined.