DIET AND GENETIC INTERACTIONS IN PROSTATE CANCER

描述：AR基因CAG重复长度的多态有 已被证明与前列腺癌的风险相关。用血 在1993-94年间，从正在进行的HPFS中的18,000名男子中收集的样本， 与口腔刷牙的结合将从额外的20,000人那里获得 队列成员，有计划表征前列腺癌的风险， 基于AR基因的CAG多态。然后，使用嵌套的 1993-2000年约1000例预测病例的病例对照设计， 特定营养因素对前列腺癌风险的影响将是 经过检查，对遗传风险进行分层。具体地说， 饮食和营养状况(成年前肥胖和达到的身高)将 根据风险分层检查男性前列腺癌的发病率 根据AR基因中CAG重复数计算。然后，将进行评估 风险较高的男性是否有可能减少他们的过度行为 通过减少动物脂肪的摄入量和通过增加 番茄红素和纤维摄入量，已经被联系在一起的饮食方面 降低了总体队列中的风险。非营养因素是 影响睾丸激素水平的假设也将被检验，在 特定的体力活动和吸烟与 根据AR按遗传风险分层的男性前列腺癌 特点。最终的目标是获取口腔涂片用于DNA分析。 来自HPFS参与者，他们之前没有提供血液样本。这 将完成大型数据库的建立，包括)更新 50,000名男性在15年内的饮食和其他暴露信息， B)储存的DNA样本(血液或口腔刷牙)约38,000份 在这些人中，c)存储了18,000名参与者的血浆，d)存档 前列腺癌的组织。口腔刷牙，以及 为本申请中的具体目标提供基础，将允许 用于快速测试未来的特定假设。

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.