Breast Cancer

在这个项目中，我们建议继续研究发生和致命乳腺癌的潜在的可改变的营养和激素风险因素，包括那些在诊断乳腺癌后影响生存的因素。这项工作将使用储存的血液和尿样、存档的DNA、重复调查问卷和护士健康研究(1976-2012年间约有10,000例浸润性乳腺癌)的长期随访。暴露也将与使用乳腺癌发病病理块的肿瘤特征有关。我们将具体研究维生素D和褪黑素与乳腺癌风险的关系，1-碳营养素的摄入量和血液水平与以全球低甲基化为特征的乳腺癌风险的关系(通过LINE-1甲基化评估)，以及酒精消费与乳腺癌发病率的变化。我们还将评估与肿瘤相关的危险因素，按多种受体的表达进行分类，并与致命性乳腺癌相关。可改变因素与乳腺癌风险的关联将在遗传风险较高的女性中进行检验，这些女性由正在进行的GWAS定义。乳腺癌的LINE-1甲基化将被评估为一个独立的预后因素，以及低体力活动和更多的 我们将研究通过胰岛素信号通路降低体重的方法。诊断后的饮食胰岛素指数和蛋白质质量将被评估为生存的预测因素。本项目与项目2和项目3有共同的生物学和机械学主题，包括维生素D、1-碳代谢的作用以及与癌症发病率和存活率有关的能量平衡，并与其他项目一样，在方法学问题上与项目4密切互动。它还与其他项目分享了强大的 核心A(队列后续行动和数据库维护)、核心B(确认癌症和死因)、核心C(生物谱管理)和核心D(领导和数据分析)提供行政和科学基础设施。这些发现应该会加强对乳腺癌病因和进展的了解，并为妇女及其卫生保健提供者努力减少这种疾病的痛苦和死亡提供指导。

In this Project, we propose to continue the investigation of potentially modifiable nutritional and hormonal risk factors for incident and fatal breast cancer, including those that affect survival after the diagnosis of breast 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 10,000 incident invasive breast cancers). Exposures will also be related to tumor characteristics using pathology blocks from incident breast cancers. We will specifically examine the relation of vitamin D and melatonin to breast cancer risk, intakes and blood levels of 1-carbon nutrients to risk of breast cancers characterized by global hypomethylation (assessed by LINE-1 methylation), and change in alcohol consumption to breast cancer incidence. We will also assess risk factors in relation to tumors classified by expression of multiple receptors and in relation to fatal breast cancer. The association of modifiable factors to risk of breast cancer will be examined among women at elevated genetic risk defined by ongoing GWAS's. LINE-1 methylation of breast cancers will be evaluated as an independent prognostic factor, and the possibility that low physical activity and greater weight reduce survival through the insulin signaling pathway will be examined. Post diagnostic dietary insulin index and protein quality will be evaluated as predictors of survival. This Project shares common biological and mechanistic themes with Projects 2, and 3, including the role of vitamin D, 1-carbon metabolism, and energy balance in relation to cancer incidence and survival, and like the other Projects interacts closely with Project 4 for methodological issues. It also shares with the other Projects a strong administrative and scientific 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 and progression of breast cancer and provide guidance for women and their health care providers in their efforts to reduce suffering and death from this disease.