Dietary and Hormonal Determinants of Cancer in Women

女性癌症的饮食和激素决定因素

• 批准号: 9098607
• 负责人: Meir Stampfer
• 金额: $ 238.63万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-12 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9098607
• 关键词: 1-Phosphatidylinositol 3-Kinase; Accounting; Address; Adopted; Aerobic; African American; Anti-Inflammatory Agents; Area; Aspirin; Behavior; Behavioral; Biological Markers; Blood; Body Weight decreased; Breast; Cancer Etiology; Case-Control Studies; Caucasians; Characteristics; Clinical; Clinical Cancer Center; Collection; Colorectal; Colorectal Adenoma; Colorectal Cancer; Colorectal Neoplasms; Complex; DNA; Data; Data Sources; Development; Diet; Emerging Technologies; Epidemiologic Studies; Etiology; Gene Expression; Gene Expression Profile; Genomics; Goals; Health; High Prevalence; Hormonal; Incidence; Inflammation; Inflammatory; Institution; Insulin Resistance; Joints; Link; Lipids; Malignant Neoplasms; Malignant neoplasm of ovary; Mammary Neoplasms; Measures; Metabolism; Metformin; Methods; Molecular; Molecular Profiling; New England; Nurses' Health Study; Obesity; Outcome; Ovarian; Participant; Pathway interactions; Prevalence; Prevention strategy; Questionnaires; Race; Research; Risk; Risk Factors; Role; Scientist; Statistical Methods; System; Systems Biology; Techniques; Technology; Testing; Time; Tissues; Training Activity; Translations; Tumor Markers; Tumor Subtype; Tumor Tissue; Urine; Vitamin D; Vitamin D Deficiency; Vitamin D supplementation; Woman; Work; adenoma; base; behavior measurement; biobank; cancer risk; cancer site; cancer survival; energy balance; follow-up; improved; innovation; insight; lipid metabolism; malignant breast neoplasm; metabolomics; new technology; novel; predictive modeling; prognostic; programs; racial difference; racial minority; randomized trial; screening; strength training; transcriptomics; tumor; tumor heterogeneity; tumor progression

DESCRIPTION (provided by applicant): While follow-up of the 121,700 women in the Nurses' Health Study (NHS) will be supported by a pending UM1 (priority score=10), this competing renewal of PO1 CA87969, "Dietary and Hormonal Determinants of Cancer in Women" continues the scientific pursuit of modifiable determinants of breast, colorectal, and ovarian cancers. A primary, cross-cutting theme is the role of metabolites and metabolomic signatures in the etiology and progression of these cancers, including developing novel statistical approaches. Further, gene expression analyses of tumor tissue will enable us to identify pathways linking risk factors to cancer. The repeated measures of behavioral factors (eg, diet) since 1976, with our extensive biorepository (blood, urine, tumor tissue), allows us to thoroughly examine relations between behavior, biomarkers, and tumor expression. Although NHS has limited racial minorities, we include research to compare prevalence of metabolomic signatures predicting breast cancer in healthy white vs black participants as a step to understand racial differences in incidence, and an Aim to collaborate with the VITAL trial to identify colorectal adenoma to test if vitamin D supplements may be particularly beneficial in blacks (building on previous research in this PO1 finding relations of vitamin D to adenoma). Briefly, Project 1 will test whether: specific metabolites and metabolomic signatures are associated with breast cancer risk and survival; metabolomics or gene expression patterns are etiologic factors underlying the relation of diet to breast cancer; energy balance and insulin resistance (eg, strength training, diet, metformin use) are associated with breast cancer risk and survival, including according to tumor expression. Project 2 will examine whether: metabolites/ metabolomic signatures are associated with colorectal cancer risk and survival; energy balance and insulin resistance are associated with colorectal cancer risk and survival, including according to tumor expression; how anti-inflammatory agents (eg, aspirin) reduce colorectal cancer, with extensive consideration of etiologic pathways; and supplemental vitamin D reduces colorectal adenoma in blacks and whites in a randomized trial. Project 3 will examine whether lipid metabolites and metabolomic signatures and inflammation-associated exposures are related to ovarian cancer, including according to tumor expression, and will initiate novel research into ovarian cancer survival. Project 4 will develop statistical approaches to analyzing metabolomics data, and to predicting cancer risk. In summary, these highly interrelated Projects will enhance our understanding of the etiology and progression of cancer and potential preventive strategies.

描述（由申请人提供）：虽然护士健康研究（NHS）中121，700名女性的随访将得到待定UM 1（优先级评分=10）的支持，但PO 1 CA 87969“女性癌症的饮食和激素决定因素”的竞争性更新继续对乳腺癌、结直肠癌和卵巢癌的可变决定因素进行科学追求。一个主要的交叉主题是代谢物和代谢组学特征在这些癌症的病因学和进展中的作用，包括开发新的统计方法。此外，肿瘤组织的基因表达分析将使我们能够确定将风险因素与癌症联系起来的途径。自1976年以来，通过我们广泛的生物储存库（血液，尿液，肿瘤组织），重复测量行为因素（例如饮食），使我们能够彻底检查行为，生物标志物和肿瘤表达之间的关系。虽然NHS的少数民族有限，但我们纳入了比较健康白色与黑人参与者中预测乳腺癌的代谢组学特征患病率的研究，作为了解发病率种族差异的一步，并旨在与VITAL试验合作，以确定结直肠腺瘤，以测试是否 维生素D补充剂可能对黑人特别有益（建立在先前的研究基础上，在此PO 1中发现维生素D与腺瘤的关系）。简而言之，项目1将测试是否： 代谢物和代谢组学特征与乳腺癌风险和生存率相关;代谢组学或基因表达模式是饮食与乳腺癌关系的潜在病因学因素;能量平衡和胰岛素抵抗（例如，力量训练、饮食、二甲双胍使用）与乳腺癌风险和生存率相关，包括根据肿瘤表达。项目2将研究：代谢物/代谢组学特征是否与结直肠癌风险和生存率相关;能量平衡和胰岛素抵抗与结直肠癌风险和生存率相关，包括根据肿瘤表达;抗炎剂如何与结直肠癌风险和生存率相关。（如阿司匹林）减少结直肠癌，广泛考虑病因途径;在一项随机试验中，补充维生素D可以减少黑人和白人的结肠直肠腺瘤。项目3将检查脂质代谢物和代谢组学特征以及炎症相关暴露是否与卵巢癌相关，包括根据肿瘤表达，并将启动对卵巢癌生存的新研究。项目4将开发统计方法来分析代谢组学数据，并预测癌症风险。总之，这些高度相关的项目将提高我们对癌症病因和进展以及潜在预防策略的理解。