Dietary and Hormonal Determinants of Cancer in Women

女性癌症的饮食和激素决定因素

• 批准号: 6859501
• 负责人: GRAHAM A. COLDITZ
• 金额: $ 462.82万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-12 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6859501
• 关键词: cancer risk; neoplasm /cancer epidemiology

DESCRIPTION (provided by applicant): The overall long-term objective of this program project is to identify novel dietary, hormonal and genetic determinants of breast (Project 1), colorectal (Project 2), and ovarian (Project 3) cancer risk in women, with the ultimate aim of finding means for prevention and improved survival. The combination of questionnaire-derived data and biomarkers, coupled with the long-term follow-up, affords the opportunity to further understand of the time course, as well as mechanisms of cancer development. To achieve these objectives, we will relate a) Prospectively collected data on diet, weight gain, physical activity, analgesic use, and other behaviors; b) Nutrient and hormone levels in prospectively collected blood; and c) Genotypic information from archived DNA and tissue blocks; to incidence of breast, colorectal, and ovarian cancers. In addition, a fourth project will refine methods for polychotomous logistic regression and, using both a previous diet validation study and a new diet validation study, will address methodologic issues involving repeated measures of nutrients in relation to cancer risk. This project will also address causal inference and incidence modeling, as well as statistical issues in haplotype estimation and haplotype-environment interactions. Additional follow-up is required to identify adequate numbers of cases to address hypotheses outlined in each of the projects. This program project is based on the Nurses' Health Study cohort, comprising 121,700 women who were 30 to 55 years of age when enrolled in 1976. The program project serves as the central resource for updating questionnaire data and confirming incident diseases necessary for the many related grants addressing incidence of cancer and other major chronic diseases. Thus, through funding of Cores A and B in the program project, we maintain follow-up of the cohort and timely confirmation of incident cancers and deaths. Core C conducts specimen handling and genetic analysis and Core D provides leadership and data analysis. The program project also helps to support our repository of biological samples. With this renewal application, we have an institutional commitment of $386,000 to upgrade our freezer facility. We address three major themes across the projects. Each project will be providing either an initial assessment (ovarian cancer) or more in depth assessment (breast and colon cancers) of the role of one carbon metabolism and gene hypermethylation in carcinogenesis. Further, modeling these complex exposures will be a focus of Project 4, hence optimizing the analyses being conducted in the other three projects. The role of energy balance throughout life (as assessed through body size, physical activity, and IGF) is another focus of the three projects. The role of inflammatory markers in disease is an area of focus in both the colon and ovarian projects. Project 4 develops statistical approaches to data analysis that apply directly to Projects 1, 2, and 3 for evaluation of nutrient-cancer associations when using repeated measures of diet. Methodologic work on polychotomous logistic regression is applicable to each project as sufficient numbers of cases allow for evaluation of hypotheses relating to subsets of cancer endpoints (e.g., ductal vs., lobular breast cancer; mucinous vs. nonmucinous ovarian cancer; total cancer mortality). Furthermore, the development of methods for haplotype estimation and the evaluation of haplotype-environment interactions are applicable across each of the projects as we evaluate potential gene-environment interactions. Strong scientific synergy permeates the projects. All projects are based on the same infrastructure of data collection, management, disease follow-up, and data analysis. The investigators, although focusing on their own areas, interact closely, which allows cross-fertilization of knowledge, ideas and approaches, and results in considerable productivity and efficiency.

描述（由申请人提供）： 该计划项目的总体长期目标是确定女性乳腺癌（项目1），结直肠癌（项目2）和卵巢癌（项目3）风险的新饮食，激素和遗传决定因素，最终目的是找到预防和提高生存率的方法。 通过将肿瘤来源的数据和生物标志物结合起来，再加上长期随访，可以进一步了解时间进程以及癌症发展的机制。 为了实现这些目标，我们将 a）Prosternal收集有关饮食、体重增加、体力活动、止痛药使用和其他行为的数据; B）预期采集的血液中的营养素和激素水平;以及 c）来自存档DNA和组织块的基因型信息;乳腺癌、结直肠癌和卵巢癌的发病率。 此外，第四个项目将完善多分类逻辑回归的方法，并使用以前的饮食验证研究和新的饮食验证研究，将解决涉及重复测量与癌症风险有关的营养素的方法学问题。 该项目还将解决因果推理和发病率建模，以及单倍型估计和单倍型环境相互作用的统计问题。 需要采取更多的后续行动，以确定足够数量的案件，以解决每个项目中概述的假设。 该方案项目以护士健康研究队列为基础，包括1976年登记时年龄在30至55岁之间的121 700名妇女。 该方案项目是更新问卷数据和确认癌症和其他主要慢性病发病率的许多相关赠款所需的偶发疾病的中心资源。 因此，通过资助项目中的核心A和B，我们保持了对队列的随访，并及时确认了癌症和死亡事件。 核心C进行标本处理和遗传分析，核心D提供领导和数据分析。 该计划项目还有助于支持我们的生物样本库。 通过这次更新申请，我们有386，000美元的机构承诺来升级我们的冷冻设施。 我们在项目中讨论了三个主要主题。 每个项目将提供一个初步评估（卵巢癌）或更深入的评估（乳腺癌和结肠癌）的作用，一碳代谢和基因超甲基化在致癌作用。 此外，对这些复杂风险进行建模将是项目4的重点，从而优化其他三个项目中进行的分析。 能量平衡在整个生命中的作用（通过身体大小，身体活动和IGF评估）是三个项目的另一个重点。 炎症标志物在疾病中的作用是结肠和卵巢项目的重点领域。 项目4开发了直接应用于项目1、2和3的数据分析的统计方法，用于在使用重复的饮食测量时评估营养与癌症的关联。 多分类逻辑回归的方法学工作适用于每个项目，因为足够数量的病例允许评估与癌症终点子集相关的假设（例如，导管与，小叶性乳腺癌;粘液性卵巢癌与非粘液性卵巢癌;总癌症死亡率）。 此外，单倍型估计和单倍型-环境相互作用的评价方法的开发适用于每个项目，因为我们评估了潜在的基因-环境相互作用。 强大的科学协同作用渗透到项目中。 所有项目都基于相同的数据收集、管理、疾病随访和数据分析基础设施。 调查人员虽然侧重于各自的领域，但相互密切交流，使知识、想法和方法得以相互促进，并产生了相当大的生产力和效率。