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.

在该项目中，我们建议继续研究出现可能改变的营养和荷尔蒙危险因素，以造成致命的乳腺癌，包括影响乳腺癌后生存的营养和荷尔蒙风险因素。这项工作将使用储存的血液和尿液样本，存档的DNA，反复的问卷调查以及护士健康研究（1976年至2012年）进行的长期随访，大约有10,000次入侵性乳腺癌）。暴露也将与肿瘤特征有关，使用事故乳腺癌的病理阻滞。我们将特别研究维生素D和褪黑激素与乳腺癌风险，1-碳养分的摄入量和血液水平与以全球甲基化为特征的乳腺癌风险（通过LINE-1甲基化评估）以及饮酒对乳腺癌发生率的变化。我们还将评估与通过多种受体表达和致命乳腺癌相关的肿瘤有关的危险因素。可修改因素与乳腺癌风险的关联将在持续的GWAS定义的遗传风险升高中检查。乳腺癌的甲基化将作为独立的预后因素进行评估，并且身体活动较低和更大的可能性 将检查重量通过胰岛素信号通路的生存率。诊断后饮食胰岛素指数和蛋白质质量将被评估为存活的预测指标。该项目与项目2和3共享共同的生物学和机械主题，包括维生素D，1-碳代谢的作用以及与癌症发病率和生存有关的能量平衡，并且与其他项目有关方法4的方法4与项目4紧密相互作用。它还与其他项目分享了强大的 核心A（队列随访和数据基础维护），B（癌症的确认和死亡原因），C（生物可能性的管理）和D（领导力和数据分析）提供的行政和科学基础设施。这些发现应增强对乳腺癌的病因和进展的理解，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。