Colorectal Cancer

在这个项目中，我们建议继续研究结直肠癌潜在的可改变的营养和激素危险因素，包括那些在诊断出结直肠癌后影响生存的因素。这项工作将使用存储的血液和尿样、存档的DNA、重复调查问卷和护士健康研究(1976-2012年间发生约2220例结直肠癌)中的长期随访，以及使用来自大约1,554例结直肠癌的病理块的肿瘤特征。我们建议研究结直肠癌的4条相互关联的途径：维生素D、能量平衡、炎症和褪黑素。为 目的1，我们建议检查维生素D状态与假设的肿瘤特征的关系，以及是否可以通过补充维生素D来采取预防措施，特别是对于血浆炎症因子水平升高的妇女。对于目标2，我们将研究一种全面的饮食胰岛素反应指标(饮食胰岛素指数)，阐明脂联素和高胰岛素血症的联合和独立作用，并识别与肥胖介导的结肠癌相关的基因。就目标3而言，我们建议 根据环氧合酶-2在腺瘤中的表达，更好地定义阿司匹林对结直肠肿瘤的化学预防，将我们的工作扩展到炎症标记物，并识别参与阿司匹林介导的化学预防的基因。此外，我们还将研究这些因素对结直肠癌切除术后生存率的独立影响。为了实现这一点，我们建议将基因改变、可修改的因素和假想的致病机制联系起来。该项目与项目2和项目3共享共同的生物学和机械学主题，包括维生素D的作用，以及与癌症发病率和 在方法问题上，与项目4密切互动。它还与其他项目共享由核心A(队列跟踪和数据库维护)、核心B(确认癌症和死因)、核心C(生物检验管理)和核心D(领导和数据分析)提供的强大的科学和行政基础设施。这些发现应该会加强对结直肠癌病因的了解，并有助于减少这种疾病的发病率和死亡率。

In this Project, we propose to continue the investigation of potentially modifiable nutritional and hormonal risk factors for colorectal cancer, including those that affect survival after the diagnosis of this cancer. This work will use the stored blood and urine samples, archived DNA, repeated questionnaires, and long follow-up in the Nurses' Health Study (1976-2012 with approximately 2,220 incident colorectal cancers), and tumor characteristics using pathology blocks from approximately 1,554 colorectal cancers. We propose to examine 4 inter-related pathways for colorectal cancer: vitamin D, energy balance, inflammation, and melatonin. For aim 1, we propose to examine vitamin D status in relation to hypothesized tumor characteristics, and if preventive actions can be taken through vitamin D supplementation, particularly for women with elevated levels of plasma inflammatory factors. For aim 2, we will examine a comprehensive dietary measure of insulin response (dietary insulin index), clarify the joint and independent effects of adiponectin, and hyperinsulinemia, and identify genes involved in obesity-mediated colon cancer. For aim 3, we propose to better define aspirin chemoprevention of colorectal neoplasia based on COX-2 expression in the incident adenoma, to extend our work to inflammatory markers, and identify genes involved in aspirin-mediated chemoprevention. We will additionally examine the independent effect of these factors on survival following a resection of colorectal cancer. To accomplish this, we propose to link genetic alterations, modifiable factors, and hypothesized pathogenic mechanisms. This Project shares common biological and mechanistic themes with Projects 2, and 3, including the role of vitamin D, and energy balance in relation to cancer incidence and survival, and interacts closely with Project 4 for methodological issues. It also shares with the other Projects a strong scientific and administrative infrastructure provided by Cores A (cohort follow-up and data base maintenance), B (confirmation of cancer and cause of death), C (management of the biospecimens) and D (leadership and data analysis). The findings should enhance understanding of the etiology of colorectal cancer and aid in efforts to reduce incidence and death from this disease.