Prospective Studies of Diet and Cancer in Men and Women

描述(由申请者提供)：这个拟议的持续计划项目将使用前瞻性收集的饮食数据、冰冻血浆和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(胶质瘤)的假说。该方案支持并依赖于对51,529名男性的持续跟踪，这些男性自1986年以来每四年完成一次广泛的饮食调查(卫生专业人员后续研究，HPFS)，并与121,700名妇女的护士健康研究(NHS)密切相关。该计划项目是NCI赞助的癌症风险基因决定因素队列联盟的创始成员，并向其提供数据和DNA样本。拟议的延续将延伸和完善最初19年的随访观察，并将解决与癌症发病率和存活率有关的新假设。交叉主题是研究维生素D、炎症和能量平衡途径，因为它们与癌症发病率有关。特别强调癌症风险和存活率的潜在可改变的决定因素。项目1检验了维生素D摄入量、血液水平、代谢基因和乳制品消费与局限性前列腺癌和致命性前列腺癌之间的关系。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、饮食胰岛素指数、血浆C肽和脂联素)的使用也将被详细检查。具体的饮食因素将与前列腺癌患者的存活率有关。项目2检查与结直肠癌和腺瘤诊断相关的维生素D血液水平、摄入量和代谢基因，包括与肿瘤的组织学和分子特征的关系。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途径对结肠癌风险的影响。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。对于乳腺癌、肺癌、结肠癌、肾癌、卵巢癌和胰腺癌，已经获得了精确和独特的信息，拟议的工作将扩大对前列腺癌、雌激素受体阴性乳腺癌和胶质瘤的分析。项目4涉及遗传多态、饮食和癌症风险的流行病学研究中的方法学问题。这些研究包括分析代谢途径中的多种多态现象，以及饮食和基因类型测量误差的影响和调整。LAV概要：这些高度相关的项目综合了饮食因素、相关的非饮食因素、血液营养和激素水平、遗传易感性以及肿瘤的分子特征。这一发现将对预防和预测男性和女性的主要癌症做出重要贡献。

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.