Genetic Risk Profiling in Metastatic Prostate Carcinoma

转移性前列腺癌的遗传风险分析

• 批准号: 6556523
• 负责人: ADAM S KIBEL
• 金额: $ 15.3万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-18 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6556523
• 关键词: biomedical equipment development; cancer risk; carcinoma; clinical research; genetic markers; genetic polymorphism; genetic registry /resource /referral center; genetic screening; genetic susceptibility; genotype; human genetic material tag; human mortality; human old age (65+); human subject; male; metastasis; neoplasm /cancer genetics; prostate neoplasms

DESCRIPTION (provided by applicant): PSA screening has contributed to a dramatic increase in the number of prostate cancer cases diagnosed and a subtle decrease in mortality from this disease. Unfortunately, many patients still present with aggressive, potentially lethal disease either because 1) the patient did not participate in a screening program, 2) the program did not identify the disease early enough for cure or 3) the treatment chosen did not eradicate the disease. At the same time, many men go through years of unnecessary screening and/or are diagnosed with prostate carcinoma with low metastatic potential. What is needed are markers to identify men, not at high risk of having prostate carcinoma, but at high risk of dying of prostate carcinoma. Identification of high risk men prior to developing the disease would allow intense screening and/or prophylaxis while sparing those at low risk years of screening. Identification of high risk men after diagnoses would allow targeted therapy while sparing those at low risk potentially morbid treatment. We believe that analysis of common polymorphic variants will allow exactly this risk stratification. The objective of this application is to identify which DNA polymorphisms that are associated with risk for metastatic prostate carcinoma and therefore are potential markers for aggressive prostate cancer. We propose to perform a case-control study to identify polymorphic variants associated with advanced prostate cancer using patients with metastatic prostate carcinoma as our cases and individuals with little or no risk of ever developing prostate carcinoma as our controls. There are two specific aims to this proposal. (I) To establish a bank of somatic DNAs from advanced prostate cancer patients and race matched controls. (II)To search for associations between genotypes and risk of advanced prostate carcinoma. The rationale for studying patients with metastatic disease is two fold. First, patients with metastatic disease unequivocally have clinically important prostate carcinoma. As a result, there are no patients with indolent disease to obscure significant associations. Second, since these are the patients in whom earlier identification has the potential to make the greatest impact, they are the patients who should be studied. At the conclusion of this study, we will have a panel of markers with the potential to predict, in future prospective studies, which patients are at high risk of eventual death from prostate carcinoma.

描述（由申请人提供）：PSA筛查已导致诊断为诊断的前列腺癌病例的数量显着增加，并导致这种疾病的死亡率细微降低。不幸的是，许多患者仍然患有侵略性，可能是致命的疾病，因为1）患者没有参加筛查计划，2）该程序没有足够早期识别该疾病以治愈或3）所选的治疗没有消除该疾病。同时，许多男性经历了多年的不必要的筛查和/或被诊断为前列腺癌具有低转移性潜力。需要的是识别男性的标记，而不是患有前列腺癌的高风险，而是死于前列腺癌的高风险。在发展疾病之前，鉴定高风险男性将允许在筛查低风险年份的情况下进行激烈的筛查和/或预防。诊断后，高风险男性的识别将允许有针对性的治疗，同时保留那些处于低风险的病态治疗的患者。我们认为，对常见多态性变体的分析将完全允许这种风险分层。该应用的目的是确定与转移性前列腺癌风险相关的DNA多态性，因此是侵袭性前列腺癌的潜在标志。我们建议进行一项病例对照研究，以鉴定使用转移性前列腺癌患者作为我们的病例，而几乎没有或根本没有发展为对照组的病例或没有风险的患者，鉴定了与晚期前列腺癌相关的多态性变异。该提案有两个具体的目标。 （i）从晚期前列腺癌患者和种族匹配的对照组中建立一系列体细胞DNA。 （ii）寻找基因型和晚期前列腺癌风险之间的关联。研究转移性疾病患者的基本原理为两倍。首先，毫无疑问的转移性疾病患者患有临床上重要的前列腺癌。结果，没有患有懒惰疾病的患者可以掩盖显着关联。其次，由于这些患者有可能产生最大影响的患者，因此他们是应该研究的患者。在这项研究结束时，我们将拥有一个标记面板，并有可能在未来的前瞻性研究中预测患者最终死于前列腺癌的高风险。