Prospective Studies of Diet and Cancer in Men and Women

描述（由申请人提供）：该拟议的持续计划项目将使用前瞻性收集的饮食数据、冷冻血浆和DNA以及肿瘤组织来解决有关前列腺癌、结肠癌和直肠癌、乳腺癌和脑癌（神经胶质瘤）的假设。该方案支持并依赖于对自1986年以来每四年完成一次广泛饮食调查表的51 529名男子的持续跟踪（卫生专业人员跟踪研究），并与对121 700名妇女的护士健康研究密切相关。该计划项目是NCI赞助的癌症风险遗传决定因素队列联盟的创始成员，并为其提供数据和DNA样本。拟议的继续将扩大和完善从第一个19年的后续行动的观察，也将解决新的假设有关的癌症发病率和生存。交叉主题是维生素D，炎症和能量平衡途径的研究，因为它们与癌症发病率有关。特别强调癌症风险和生存的潜在可改变的决定因素。项目1研究了维生素D摄入量、血液水平、代谢基因和乳制品消费与局部和致命前列腺癌相关的假设。还将详细检查他汀类药物、阿司匹林和非甾体抗炎药的使用以及胰岛素血症（体重和体重增加、膳食胰岛素指数、血浆C肽和脂联素）。具体的饮食因素将在与前列腺癌的男性生存。项目2检查维生素D血液水平，摄入量和代谢基因与结直肠癌和腺瘤的诊断，包括与肿瘤的组织学和分子特征的关联。还将评估抗炎药的使用及其与相关基因多态性的相互作用，以及胰岛素、脂联素和IFG-1途径与结肠癌风险的相互作用。具体的饮食因素，体重变化，体力活动和抗炎药的使用将与结直肠癌患者的生存率相关。项目3汇集了21项关于饮食和癌症的主要前瞻性研究的数据。已经获得了乳腺癌、肺癌、结肠癌、肾癌、卵巢癌和胰腺癌的精确和独特的信息，拟议的工作将扩展到前列腺癌、雌激素受体阴性乳腺癌和神经胶质瘤的分析。项目4涉及遗传多态性、饮食和癌症风险的流行病学研究中的方法问题。这些包括分析代谢途径中的多种多态性，以及饮食和基因型中测量误差的影响和调整。LAV总结：这些高度相关的项目整合了饮食因素，相关的非饮食因素，血液营养和激素水平，遗传易感性和肿瘤的分子特征。这些发现将对男性和女性主要癌症的预防和预后做出重要贡献。

DESCRIPTION (provided by applicant): This proposed continuing Program Project will use prospectively collected dietary data, frozen plasma and DNA, and tumor tissue to address hypotheses regarding cancers of the prostate, colon and rectum, breast, and brain (glioma). This Program supports, and depends on, the continued follow-up of 51,529 men who have completed extensive dietary questionnaires every four years since 1986 (the Health Professionals Follow-up Study, HPFS), and is also closely linked to the Nurses' Health Study (NHS) of 121,700 women. The Program Project is a founding member of, and contributes data and DNA samples to; the NCI sponsored Cohort Consortium on genetic determinants of cancer risk. The proposed continuation will extend and refine observations from the first 19 years of follow-up and will also address new hypotheses related to both cancer incidence and survival. Cross-cutting themes are the investigation of vitamin D, inflammatory, and energy balance pathways as they relate to cancer incidence. Particular emphasis is given to potentially modifiable determinants of cancer risk and survival. Project 1 examines hypotheses relating vitamin D intakes, blood levels, and metabolizing genes and consumption of dairy products to both localized and fatal prostate cancer. Use of statins, aspirin, and NSAID's and of insulinemia (weight and weight gain, dietary insulin index, plasma C-peptide, and adiponectin) will also be examined detail. Specific dietary factors will be addressed in relation to survival among men with prostate cancer. Project 2 examines vitamin D blood levels, intakes, and metabolizing genes in relation to the diagnosis of colorectal cancer and adenomas, including associations with histological and molecular characteristics of tumors. The use of anti-inflammatory agents and their interactions with polymorphisms in related genes, and of insulin, adiponectin, and IFG-1 pathways to risk of risk of colon cancer will also be evaluated. Specific dietary factors, weight change, physical activity, and use of anti-inflammatory agents will be examined in relation to survival among patients with colorectal cancer. Project 3 pools data from 21 major prospective studies of diet and cancer. Precise and unique information has already been obtained for breast, lung, colon, kidney, ovarian, and pancreatic cancer, and the proposed work will extend analyses to prostate cancer, estrogen receptor negative breast cancer, and gliomas. Project 4 addresses methodological issues in epidemiological studies of genetic polymorphisms, diet and risk of cancer. These include the analysis of multiple polymorphisms within metabolic pathways and the effects of, and adjustment for, measurement errors in both diet and genotypes. Lav summary: These highly interrelated projects integrate dietary factors, related non-dietary factors, blood nutrient and hormone levels, genetic susceptibility, and molecular characteristics of tumors. The findings will contribute importantly to the prevention and prognosis of major cancers of men and women.