Colorectal Neoplasia in SELECT Participants

描述（由申请人提供）：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CRC的良性肿瘤前体，尽管大多数CRA不会进展为CRC，并且并非所有结直肠息肉都是腺瘤。在既往有CRA的患者中，复发性CRA的发生率为每年10-15%，并作为CRC化学预防试验的终点。相当多的间接证据支持硒对CRC的化学预防作用。SELECT试验将在35，584名随机男性受试者中评估硒（如L-硒代蛋氨酸）和维生素E单独和联合对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CRC发病率和无CRC生存率的影响。当前申请的长期目的是解决母SELECT试验的CRC相关次要目的。具体目的是测量SELECT干预措施对SELECT参与者CRA患病率的影响，并同时比较这些干预措施对本研究人群CRC发病率和CRA患病率的影响。CRA患病率将根据SELECT受试者的手术和组织病理学报告确定，这些受试者在试验期间接受了下胃肠道内窥镜检查（乙状结肠镜检查或结肠镜检查）和结直肠息肉切除术，作为其常规临床护理的一部分。CRC发生率将根据已经实施的SELECT试验方案确定，以确定参与者在试验期间诊断的所有非前列腺癌。本申请的主要研究者（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SELECT试验和CCPPP基础设施将用于所有数据收集和分析，从而节省大量成本。拟定的SELECT受试者结直肠肿瘤（CRA和CRC）研究的一个独特方面是有机会在同一（SELECT）研究人群中研究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未回答的问题：防止结直肠腺瘤复发的药物是否也能预防结直肠癌？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.