Colorectal Neoplasia in SELECT Participants

描述(申请人提供)：结直肠癌(CRC)是美国癌症死亡的第二大原因。腺瘤性息肉或结直肠腺瘤(CRA)是大肠癌的良性肿瘤先兆，尽管大多数CRA不会进展为CRC，而且并不是所有的大肠息肉都是腺瘤。在既往有CRA的患者中，复发的CRA以每年10-15%的速度发展，并作为CRC化学预防试验的终点。大量间接证据支持硒对结直肠癌的化学预防作用。这项选定的试验将评估硒，如L-硒蛋氨酸，以及维生素E单独和联合使用对35,584名现已随机分配的男性受试者前列腺癌临床发病率的影响。SELECT计划的次要目标包括评估硒和维生素E对结直肠癌发病率和无结直肠癌生存率的影响。本申请的长期目标是解决父母选择试验与儿童权利公约有关的次要目标。具体目的是测量选定干预措施对选定参与者中CRA患病率的影响，并同时比较这些干预措施对本研究人群中CRC发病率和CRA患病率的影响。CRA患病率将根据选定参与者的程序和组织病理学报告确定，这些参与者在试验期间接受低位胃肠内窥镜检查(乙状结肠镜或结肠镜检查)和切除结直肠息肉，作为其常规临床护理的一部分。CRC发病率将从一项已经到位的精选试验方案中确定，以确定在试验期间在参与者中诊断出的所有非前列腺癌。本申请的主要研究人员(PI)也是结肠癌预防计划项目(CCPPP)的PI，该项目包括一项多中心III期随机硒CRA复发试验。现有的精选试验和CCPPP基础设施将用于所有数据收集和分析，从而节省大量费用。拟议在选定参与者中进行的结直肠肿瘤(CRA和CRCs)研究的一个独特方面是，有机会在同一(选定)研究人群中调查试验干预对结直肠腺瘤和癌症终点的影响。这项研究解决了一个主要的悬而未决的问题：预防结直肠腺瘤复发的药物也可以预防结直肠癌吗？这个问题是在已经建立的临床试验的背景下解决的。

DESCRIPTION (provided by applicant): Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. Adenomatous polyps or colorectal adenomas (CRAs) are the benign neoplastic precursors of CRCs, although most CRAs do not progress to CRC and not all colorectal polyps are adenomas. Recurrent CRAs develop at a rate of 10-15% per year in patients with previous CRAs and serve as endpoints in CRC chemoprevention trials. Considerable indirect evidence supports a chemopreventive role for selenium against CRC. The SELECT Trial will assess the effect of selenium, as L-selenomethionine, and vitamin E alone and in combination on the clinical incidence of prostate cancer in 35,584 now-randomized male subjects. Planned secondary objectives of SELECT include assessment of the effect of selenium and vitamin E on CRC incidence and CRC-free survival. The long-term objective of the current application is to address the CRC-related secondary objectives of the parent SELECT Trial. Specific Aims are to measure the effects of SELECT interventions on CRA prevalence in SELECT participants and to compare concurrently the effects of treatment with these interventions on CRC incidence and CRA prevalence in this study population. CRA prevalence will be determined from the procedure and histopathology reports of SELECT participants who undergo lower gasatrointestinal endoscopy (sigmoidoscopy or colonoscopy) and removal of colorectal polyps as part of their usual clinical care while in the trial. CRC incidence will be determined from a SELECT Trial protocol already in place to ascertain all non-prostate cancers diagnosed in participants while in the trial. The Principle Investigator (PI) of this application is also PI of the Colon Cancer Prevention Program Project (CCPPP), which includes a multi-center Phase III randomized selenium CRA recurrence trial. Existing SELECT Trial and CCPPP infrastructure will be utilized for all data collection and analyses, with consequent substantial cost savings. A unique aspect of the proposed study of colorectal neoplasia (CRAs and CRCs) in SELECT participants is the opportunity to investigate the effects of trial interventions on colorectal adenoma and cancer endpoints in the same (SELECT) study population. This study addresses a major unanswered question: Do agents that prevent recurrence of colorectal adenomas also prevent colorectal cancer? The question is addressed in the context of an already established clinical trial.