DIET AND GENETIC INTERACTIONS IN PROSTATE CANCER

描述：AR基因中CAG重复序列长度的多态性， 与前列腺癌的发病风险有关。 使用血液 1993- 1994年从正在进行的HPFS中的18，000名男性中收集的样本， 与口腔刷相结合，将从另外20，000人中获得 队列成员，有计划描述前列腺癌的风险， 基于AR基因的CAG多态性。 然后，使用嵌套的 对1993-2000年约1 000例预测病例进行病例对照设计， 特定营养因素对前列腺癌风险的影响将是 检查，对遗传风险进行分层。 具体而言， 饮食和营养状况（成年前肥胖和身高）将 检查按风险分层的男性前列腺癌发病率 根据AR基因中CAG重复序列的数目， 然后，评估将 高风险的男性是否可以减少他们的过量摄入， 通过减少动物脂肪的消耗和增加 番茄红素和纤维的摄入，饮食方面已经与 在整个队列中风险降低。 非营养因素， 假设影响睾酮水平也将被检查， 特别是体力活动和吸烟，与 男性前列腺癌，根据AR按遗传风险分层 特色 最后一个目标是获得用于DNA分析的口腔涂片 来自之前未提供血液样本的HPFS受试者。 这 将完成建立一个大型数据库，包括： 50，000名男性在15年期间的饮食和其他接触信息， B）储存的DNA样本（血液或口腔刷拭），来自约38，000 在这些人中，c）储存了18，000名参与者的血浆，d）存档 前列腺癌的组织 口腔刷，沿着 为本申请中的具体目标提供基础，将允许 以快速检验未来的具体假设。

DESCRIPTION: Polymorphisms in the CAG repeat length in the AR gene have been demonstrated to correlate with risk of prostate cancer. Using blood samples collected in 1993-94 from 18,000 men in the ongoing HPFS, in combination with buccal brushings to be acquired from an additional 20,000 cohort members, there are plans to characterize risk of prostate cancer, based on CAG polymorphisms in the AR gene. Then, using a nested case-control design of approximately 1,000 projected cases from 1993-2000, the impact of specific nutritional factors on prostate cancer risk will be examined, stratifying across genetic risk. Specifically, associations of diet and nutritional status (pre-adult adiposity and attained height) will be examined with incidence of prostate cancer among men stratified by risk according to number of CAG repeats in the AR gene. Then, an assessment will be made of whether men at higher risk can potentially reduce their excess risk by decreasing their consumption of animal fat and by increasing lycopene and fiber intake, aspects of diet that have already been associated with reduced risk in the overall cohort. Non-nutritional factors that are hypothesized to influence testosterone levels will also be examined, in particular physical activity and smoking, in relation to incidence of prostate cancer among men, stratified by genetic risk according to AR characteristics. A final Aim is to acquire buccal smears for DNA analyses from HPFS participants who did not previously provide blood specimens. This will complete the establishment of a large database consisting of a) updated dietary and other exposure information over a 15 year period for 50,000 men, b) stored DNA samples (blood or buccal brushing) from approximately 38,000 of these men, c) stored plasma from 18,000 participants, and d) archived tissue from incident prostate cancers. The buccal brushings, along with providing the basis for the specific aims in this application, will allow for the rapid testing of future specific hypotheses.