Dietary and Hormonal Determinants of Cancer in Women

描述(由申请者提供)：虽然护士健康研究(NHS)中121,700名女性的随访将得到UM1(优先分数=10)的支持，但PO1 CA87969的这一竞争性更新，“女性癌症的饮食和激素决定因素”，继续对乳腺癌、结直肠癌和卵巢癌的可改变决定因素的科学追求。一个主要的交叉主题是代谢物和代谢组特征在这些癌症的病因和进展中的作用，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，行为因素(如饮食)的反复测量，加上我们广泛的生物库(血液、尿液、肿瘤组织)，使我们能够彻底检查行为、生物标记物和肿瘤表达之间的关系。尽管英国国民健康保险制度的少数族裔人数有限，但我们的研究包括比较健康的白人和黑人参与者中预测乳腺癌的代谢特征的患病率，作为了解发病率种族差异的一步，并旨在与VITAL试验合作识别结直肠腺瘤，以测试是否 维生素D补充剂可能对黑人特别有益(建立在本PO1之前发现维生素D与腺瘤关系的研究基础上)。简而言之，项目1将测试是否：特定 代谢产物和代谢组特征与乳腺癌风险和生存相关；代谢组学或基因表达模式是饮食与乳腺癌关系的病因因素；能量平衡和胰岛素抵抗(如力量训练、饮食、二甲双胍使用)与乳腺癌风险和生存相关，包括与肿瘤表达有关。项目2将检测：代谢物/代谢组学特征是否与结直肠癌风险和生存相关；能量平衡和胰岛素抵抗是否与结直肠癌风险和生存相关，包括与肿瘤表达有关；抗炎药(如阿司匹林)如何在广泛考虑病因途径的情况下降低结直肠癌；以及在一项随机试验中，补充维生素D如何减少黑人和白人的结直肠癌。项目3将研究脂质代谢产物和代谢组特征以及炎症相关暴露是否与卵巢癌有关，包括与肿瘤表达有关，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加强我们对癌症的病因和进展以及潜在的预防策略的了解。

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.