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: 8555228
• 负责人: GREGORY S. COOPER
• 金额: $ 28.14万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-14 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8555228
• 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; Screening procedure; 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

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.

结直肠癌在很大程度上是可以预防的，通过使用筛查和切除前病变， 腺瘤虽然结肠镜检查是最常用的筛查试验，但最近的研究表明， 怀疑其预防右侧癌症的有效性。此外，有相当大比例的 拒绝结肠镜检查或结肠镜检查不容易获得的合格患者。异常检测 粪便DNA（sDNA）中的分子/遗传标记物正在成为结肠镜检查的有希望的替代物。的 目前可用的sDNA测试检测波形蛋白基因的异常甲基化，并已报道80-85%的 检测结直肠癌的敏感性。新开发的下一代sDNA检测， 与波形蛋白互补的其他甲基化DNA标记物有望更敏感， 特定.然而，这些较新的标记物尚未在筛查人群中得到验证， sDNA检测对晚期腺瘤的有效性，因此对结肠直肠癌的预防是有限的。 因此，我们提出了一个前瞻性的筛选研究，系统地评估准确性和临床 该多标记物组sDNA检测用于检测晚期腺瘤的相关性。具体来说，我们的研究 目的：1）评价sDNA检测的性能特征，并与粪便检测进行比较 免疫化学试验（FIT）用于检测无症状平均风险的晚期腺瘤 筛选群体; 2）确定组织和粪便基因异常之间的一致性/不一致性 晚期腺瘤患者中的甲基化; 3）研究在晚期腺瘤患者中的阳性sDNA检测的持续性。 切除晚期腺瘤; 4）评估漏诊或隐匿性结肠和上结肠癌的频率 在结肠镜检查正常但sDNA检测持续阳性的患者中发生胃肠道肿瘤。这些 目标将在一项对1,600名接受筛查的平均风险患者进行的比较研究中实现 结肠镜检查这个项目是高度翻译和信息从这项研究中获得的可能有重大意义 以及对结肠直肠癌筛查和一级预防的临床实践的直接影响， 以及对晚期腺瘤患者的监测。