Dietary and Hormonal Determinants of Cancer in Women

描述（由申请人提供）：该计划项目的长期目标是确定女性癌症风险（特别是乳腺癌，结肠直肠癌和卵巢癌）的新激素，饮食和遗传决定因素，目的是找到预防和提高生存率的方法。问卷调查数据、血液和尿液样本以及石蜡包埋的肿瘤组织的可用性，加上长达36年的随访，为进一步了解癌症发展的时间进程以及机制提供了机会。交叉主题包括维生素D和褪黑激素，能量平衡和炎症途径的研究，以及致命结果和肿瘤分子特征的检查。 在项目1中，我们将研究维生素D、褪黑激素和饮食摄入量（包括1碳营养素和酒精摄入量的变化）与乳腺癌风险的关系;此外，还将评估临床相关肿瘤亚型和致命疾病的风险因素。我们将评估可改变因素对高遗传风险妇女发病率的影响。此外，还将评估能量平衡在生存中的作用。 在项目2中，我们将评估维生素D和褪黑激素，包括与肿瘤特征的关联。将评估胰岛素、脂联素和胰岛素样生长因子以及炎症标志物在结肠癌发病率和生存率中的作用。在项目3中，我们将评估维生素D、褪黑激素、饮食因素（类黄酮、乳糖和丙烯酰胺）和血浆炎症标志物与卵巢癌风险的关系。此外，我们将评估肿瘤标志物与卵巢癌风险因素的关系，以及致命性疾病的风险因素。在项目4中，我们将扩展和应用分析方法，这些方法将改善我们对影响生命中不同时期风险的累积暴露的建模，在复杂的肿瘤生物标志物环境中扩展多分类逻辑回归模型，并改善乳腺癌和结肠癌风险预测模型的评估。 这一应用是基于护士健康研究队列，包括1976年30至55岁的121 700名妇女。通过对核心研究的资助，我们对队列进行跟踪，确认癌症和死亡事件，监督生物标志物的获取和使用，并提供领导和数据分析。通过该计划项目资助的护士健康研究有助于NCI赞助的队列联盟，属于其他12个联盟，并在过去5年中为30多个外部合作者提供了研究平台。

DESCRIPTION (provided by applicant): The long-term objective of this Program Project is to identify novel hormonal, dietary and genetic determinants of cancer risk (specifically breast, colorectal, and ovarian cancers) in v\/omen, with the aim of finding means for prevention and improved survival. The availability of questionnaire data, blood and urine samples and paraffin-embedded tumor tissue, coupled with up to 36 years follow-up, affords the opportunity to further understand the time course, as well as mechanisms of cancer development. Cross-cutting themes include the investigation of vitamin D and melatonin, energy balance and inflammatory pathways, as well as the examination of fatal outcomes and the molecular characterization of tumors. In Project 1, we will examine vitamin D, melatonin, and dietary intake (including 1-carbon nutrients and change in alcohol intake) in relation to breast cancer risk; further, risk factors for clinically relevant tumor subtypes and fatal disease will be assessed. We will assess the contribution of modifiable factors to incidence in women at high genetic risk. Further the role of energy balance in survival will be assessed. In Project 2, we will assess vitamin D and melatonin, including associations with tumor characteristics. The roles of insulin, adiponectin and insulin-like growth factors as well as inflammation markers in colon cancer incidence and survival will be assessed, in Project 3, we will evaluate vitamin D, melatonin, dietary factors (flavonoids, lactose and acrylamide) and plasma markers of inflammation in relation to ovarian cancer risk. Further, we will assess tumor markers in relation to ovarian cancer risk factors, as well as risk factors for fatal disease. In Project 4, we will extend and apply analytic methods that will improve our modeling of cumulative exposures that influence risk at different times in life, extend polytomous logistic regression models in a complex tumor biomarker setting, and improve evaluation of breast and colon cancer risk prediction models. This application is based on the Nurses' Health Study cohort, comprising 121,700 women who were 30 to 55 years of age in 1976. Through funding of the Cores, we maintain follow-up of the cohort and confirmation of incident cancers and deaths, oversee acquisition and use of biomarkers and provide leadership and data analysis. The Nurses' Health Study as funded through this Program Project contributes to the NCI sponsored Cohort Consortium, belongs to 12 other consortia and has served as the research platform for over 30 outside collaborators over the last 5 years.