Breast Cancer

乳腺癌

• 批准号: 7786693
• 负责人: Walter C. Willett
• 金额: $ 242.7万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7786693
• 关键词: Accounting; Address; Adult; Affect; Age; Age at Menarche; Age-Years; Alcohol consumption; Alcohols; Alleles; Amino Acids; Archives; Biological; Biological Markers; Blood; Blood specimen; Body mass index; Breast; Cancer Center; Cancer Etiology; Cancer Patient; Carbon; Carotenoids; Cause of Death; Cells; Cessation of life; Characteristics; Cheek structure; Clinical; Cohort Studies; Collaborations; Creativeness; DNA; Data Analyses; Data Collection; Databases; Development; Diagnosis; Diagnostic; Diet; Dietary Factors; Disease; ERBB2 gene; Enrollment; Environment; Erythrocytes; Estrogen Receptors; Etiology; Excretory function; Fiber; Folic Acid; Food Supply; Funding; Genetic Polymorphism; Genetic Risk; Health Personnel; Height; Hormonal; Hormonal Risk Factor; Hormone Receptor; Hormones; Incidence; Insulin; Insulin Receptor; Insulin Signaling Pathway; Intake; Investigation; Lactation; Leadership; Life; Maintenance; Malignant Neoplasms; Malignant neoplasm of prostate; Mammary Neoplasms; Measures; Melatonin; Menopause; Meta-Analysis; Metabolism; Methylation; Nurses' Health Study; Nutrient; Nutritional; Nutritional status; Participant; Pathology; Physical activity; Physicians; Plasma; Postmenopause; Premenopause; Process; Productivity; Prognostic Factor; Prospective Studies; Proteins; Questionnaires; RXR; Receptor, Melatonin, MT1; Recurrence; Repetitive Sequence; Reproduction spores; Research; Research Infrastructure; Risk; Risk Factors; Role; Sampling; Site; Source; Students; Time; Tumor Subtype; Urine; Variant; Vitamin D; Vitamin D3 Receptor; Weight; Weight Gain; Woman; Work; alcohol risk; breast cancer diagnosis; cancer diagnosis; cancer recurrence; cancer risk; cohort; diet and cancer; energy balance; experience; follow-up; fruits and vegetables; genome wide association study; genome-wide; high risk; improved; indexing; insulin sensitivity; lifestyle factors; malignant breast neoplasm; member; methyl group; modifiable risk; mortality; nutrition; operation; parity; prospective; protein expression; receptor; reproductive; response; saturated fat; tool; tumor; urinary

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.

在这个项目中，我们建议继续调查潜在的可改变的营养和激素风险因素的事件和致命的乳腺癌，包括那些影响乳腺癌诊断后的生存。这项工作将使用储存的血液和尿液样本，存档的DNA，重复的问卷调查，以及护士健康研究（1976- 2012年，约10，000例浸润性乳腺癌）的长期随访。暴露也将与肿瘤特征相关，使用来自偶发乳腺癌的病理组织块。我们将专门研究维生素D和褪黑激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），以及饮酒量与乳腺癌发病率的变化。我们还将评估与多种受体表达分类的肿瘤相关的风险因素，以及与致命性乳腺癌相关的风险因素。将在正在进行的GWAS定义的遗传风险升高的妇女中检查可改变因素与乳腺癌风险的关联。乳腺癌的LINE-1甲基化将作为一个独立的预后因素进行评估，而低体力活动和更大的 将检查通过胰岛素信号传导途径的体重减轻存活率。诊断后饮食胰岛素指数和蛋白质质量将作为生存预测因子进行评价。该项目与项目2和项目3共享共同的生物学和机制主题，包括维生素D的作用，1-碳代谢和能量平衡与癌症发病率和生存率的关系，并像其他项目一样与项目4密切互动的方法问题。它还与其他项目共享一个强大的 核心A（队列随访和数据库维护）、核心B（癌症和死因确认）、核心C（生物标本管理）和核心D（领导和数据分析）提供的行政和科学基础设施。这些发现应该加强对乳腺癌病因和进展的理解，并为妇女及其医疗保健提供者提供指导，以减少这种疾病的痛苦和死亡。