Detection of Advanced Adenoma Via Stool DNA (sDNA) Methylation Testing

通过粪便 DNA (sDNA) 甲基化检测检测晚期腺瘤

• 批准号: 8711343
• 负责人: GREGORY S. COOPER
• 金额: $ 26.14万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8711343
• 关键词: Advisory Committees; American Cancer Society; Carcinoma; Characteristics; Choristoma; Colon Carcinoma; Colonic Neoplasms; Colonoscopy; Colorectal; Colorectal Cancer; Colorectal Neoplasms; Comparative Study; Complement; DNA; DNA Markers; DNA Methylation; Data; Detection; Effectiveness; Excision; Feces; Frequencies; Genes; Genetic Markers; Gold; Guidelines; Health system; Individual; Laboratories; Large Intestine Carcinoma; Lesion; Licensing; Malignant Neoplasms; Methylation; Molecular Genetics; Neoplasms; Patients; Performance; Polypectomy; Population; Primary Prevention; Recruitment Activity; Recurrence; Reporting; Risk; Science; Side; Specificity; Testing; Tissues; Uncertainty; United States; University Hospitals; Vimentin; adenoma; clinical efficacy; clinical practice; clinically relevant; colorectal cancer prevention; colorectal cancer screening; efficacy evaluation; gastrointestinal; indexing; next generation; novel marker; population based; prevent; prospective; screening

Colorectal carcinoma is largely preventable through the use of screening and removal of the precursor lesion, adenomas. Although colonoscopy is the most commonly used screening test, recent studies have cast serious doubt about its effectiveness in preventing right sided cancer. Furthermore, there is a significant proportion of eligible patients who decline colonoscopy or in whom colonoscopy is not readily available. Testing for aberrant molecular/genetic markers in stool DNA (sDNA) is emerging as a promising alternative to colonoscopy. The currently available sDNA test detects aberrant methylation of the vimentin gene and has reported an 80-85% sensitivity for the detection of colorectal carcinoma. A newly developed next-generation sDNA test with 3 additional methylated DNA markers that are complementary to vimentin promises to be more sensitive and specific. However, these newer markers have not been validated in a screening population and data on the efficacy of sDNA testing for advanced adenomas, hence prevention of colorectal cancer, are limited. Therefore, we propose a prospective screening study to systematically evaluate the accuracy and clinical relevance of this multi-marker panel sDNA testing for detecting advanced adenomas. Specifically, our study aims to: 1) evaluate the performance characteristics of sDNA testing and compare that to the fecal immunochemical test (FIT) for the detection of advanced adenomas in an asymptomatic average-risk screening population; 2) determine the concordance/discordance between tissue and stooi gene aberrant methylation in patients with advanced adenomas; 3) investigate the persistence of positive sDNA testing after removal of advanced adenomas; and 4) assess the frequency of missed or occult colonic and upper gastrointestinal neoplasia in patients with a normal colonoscopy but persistently positive sDNA testing. These aims will be accomplished in a comparative study of 1,600 average risk patients undergoing screening colonoscopy. This project is highly translational and information gained from this study may have significant and immediate implication for the ciinical practice of screening and primary prevention of colorectal cancer, and surveillance of patients with advanced adenomas.

通过使用筛查和去除前体病变，可以预防结直肠癌 腺瘤。尽管结肠镜检查是最常用的筛查测试，但最近的研究对 怀疑它在防止右侧癌中的有效性。此外，有很大一部分 拒绝结肠镜检查或结肠镜检查的符合条件的患者。测试异常 粪便DNA（SDNA）中的分子/遗传标记正在成为结肠镜检查的有前途的替代方案。这 目前可用的SDNA测试检测波形蛋白基因的异常甲基化，并报告了80-85％ 检测结直肠癌的敏感性。一个新开发的下一代SDNA测试3 与波形蛋白互补的其他甲基化的DNA标记有望更敏感，并且 具体的。但是，这些较新的标记尚未在筛选人群中得到验证，并获得了有关的数据 SDNA测试对晚期腺瘤的功效，因此预防结直肠癌。 因此，我们提出了一项前瞻性筛查研究，以系统地评估准确性和临床 该多标记面板SDNA测试的相关性用于检测晚期腺瘤。具体来说，我们的研究 目的是：1）评估SDNA测试的性能特征，并将其与粪便进行比较 免疫化学测试（FIT），用于检测无症状平均风险中晚期腺瘤 筛查人口； 2）确定组织和Stooi基因异常之间的一致性/不一致 晚期腺瘤患者的甲基化； 3）研究阳性SDNA测试的持续性 去除晚期腺瘤； 4）评估错过或神秘结肠和上部的频率 正常结肠镜检查但持续的SDNA测试的患者的胃肠道肿瘤。这些 目标将在1,600名平均风险患者进行筛查的比较研究中实现 结肠镜检查。该项目是高度转化的，从这项研究中获得的信息可能具有重要的 以及对筛查和初级预防结直肠癌的临时实践的直接影响， 并监视晚期腺瘤患者。