DIET, EXOGENOUS HORMONES, AND BREAST CANCER RISK

饮食、外源激素和乳腺癌风险

• 批准号: 7630019
• 负责人: Walter C. Willett
• 金额: $ 45.23万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7630019
• 关键词: Address; Adipose tissue; Age; Alcohol consumption; Animals; Antioxidants; Archives; BRCA1 gene; Blood; Blood specimen; Carbon; Cessation of life; Characteristics; Choline; Cysteine; Data; Data Collection; Diagnosis; Diet; Dietary Factors; Estrogen Receptor 1; Estrogens; Fatty acid glycerol esters; Fiber; Folate; Funding; Gene-Modified; Genes; Genetic Polymorphism; Genotype; Glutamate-Cysteine Ligase; Glutathione; Health Personnel; Hormonal; Hormones; Incidence; Insulin Resistance; Intake; Life; Life Style; Ligase Gene; Malignant Neoplasms; Measures; Menarche; Metabolism; Methionine; Methylation; Methylenetetrahydrofolate reductase (NADPH); Normal Horse Serum; Numbers; Nurses' Health Study; Nutritional status; Obesity; Operative Surgical Procedures; Outcome; Overweight; Pathology; Pathway interactions; Pattern; Physical activity; Plasma; Postmenopause; Progesterone; Progestins; Prospective Studies; Questionnaires; Receptor Gene; Replacement Therapy; Risk; Sampling; Series; Somatotype; Source; Vegetables; Vitamin B 12; Vitamin B6; Walking; Woman; Work; adiponectin; base; breast cancer diagnosis; cancer recurrence; cancer risk; cohort; cyclin D2; design; diet and cancer; energy balance; follow-up; gene environment interaction; genetic analysis; hormone therapy; insulin sensitizing drugs; malignant breast neoplasm; member; programs; prospective; tumor

We propose to evaluate a series of hypotheses relating specific aspects of energy balance, onecarbon metabolism, other dietary factors, and postmenopausal hormone use to breast cancer incidence, and to survival among women with breast cancer. We will also examine associations between functionally important polymorphisms and risk of breast cancer and potential interactions between specific genotypes and diet or hormones. This work will use the stored blood samples, archived DMA, repeated questionnaires, and the long follow-up in the Nurses' Health Study (1976- 2006). Exposures will also be related to tumor characteristics using pathology blocks that have already been collected from incident breast cancer cases. We will specifically examine intensity and duration of physical activity, body build before menarche, and plasma levels of adiponectin (an insulin sensitizer) in relation to breast cancer risk. We hypothesize that low availability of 1-carbon groups, assessed by dietary and/or blood levels of folate, vitamin B-12, choline, and methionine, and by reduced-activity genotypes of methylenetetrahydrofolate reductase, are associated with breast cancers with a methylated BRCA-1 gene. We further hypothesize that breast cancer risk remains elevated among long term past users of combined estrogen plus progestin replacement therapy, and that polymorphisms in the ER and PR genes modify the relation between hormone use and breast cancer. Further, we hypothesize that dietary animal fat increases, and that vegetable fat, vegetables, fiber and walking reduces adverse outcomes after breast cancer. Because of the prospective design, long follow-up, and large number of cases, these analyses will provide important data for women and their health care providers attempting to reduce risk of breast cancer.

我们建议评估一系列与能量平衡的特定方面有关的假设， 代谢、其他饮食因素和绝经后激素使用与乳腺癌的关系 发病率和乳腺癌妇女的生存率。我们还将研究 功能上重要的多态性与乳腺癌风险之间的相互作用 基因型和饮食或激素之间的联系这项工作将使用储存的血液样本， 存档的DMA，重复的问卷调查，以及护士健康研究（1976- 2006年）。暴露也将与使用具有以下特征的病理学块的肿瘤特征相关： 已经从乳腺癌病例中收集到了。 我们将特别检查体力活动的强度和持续时间，初潮前的身体状况， 以及脂联素（一种胰岛素增敏剂）的血浆水平与乳腺癌风险的关系。我们 假设通过膳食和/或血液叶酸水平评估1-碳基团的低可用性， 维生素B-12、胆碱和蛋氨酸，以及亚甲基四氢叶酸活性降低的基因型 还原酶与BRCA-1基因甲基化的乳腺癌相关。我们进一步 假设乳腺癌的风险在过去长期使用联合化疗的患者中仍然升高， 雌激素加孕酮替代疗法，以及ER和PR基因多态性修饰 激素使用与乳腺癌的关系此外，我们假设膳食动物脂肪 增加，植物脂肪，蔬菜，纤维和步行减少乳腺癌后的不良后果 癌 由于前瞻性设计、长期随访和大量病例，这些分析将 为试图降低乳腺癌风险的妇女及其卫生保健提供者提供重要数据， 癌