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

结直肠癌在很大程度上可以通过使用筛查和切除前驱病变来预防， 腺瘤。虽然结肠镜检查是最常用的筛查方法，但最近的研究表明 怀疑它在预防右侧癌症方面的有效性。此外，有相当大比例的 拒绝接受结肠镜检查或结肠镜检查不容易获得的合格患者。检测异常 粪便DNA分子/遗传标记(SDNA)是一种很有前途的结肠镜检查替代方法。这个 目前可用的sDNA测试检测到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。一种新开发的下一代sDNA检测方法 补充波形蛋白的额外甲基化DNA标记有望更敏感和 具体的。然而，这些较新的标记尚未在筛查人群和数据中得到验证 SDNA检测对晚期腺瘤的疗效有限，因此可以预防结直肠癌。 因此，我们提出了一项前瞻性筛查研究，以系统地评估其准确性和临床应用。 多标记单链DNA检测与检测晚期腺瘤的相关性。具体来说，我们的研究 目的：1)评估sDNA检测的性能特点，并与粪便进行比较 免疫化学试验(FIT)检测无症状平均风险的晚期腺瘤 筛查人群；2)确定组织与粪便基因突变的一致性/不一致性 晚期腺瘤患者的甲基化；3)调查sDNA检测阳性的持久性 晚期腺瘤的切除；以及4)评估漏诊或隐匿性结肠和上部的频率。 结肠镜检查正常但sDNA检测持续阳性的患者中的胃肠道肿瘤。这些 目标将通过对1600名接受筛查的平均风险患者进行比较研究来实现 结肠镜检查。这个项目是高度翻译的，从这个研究中获得的信息可能会有重要的意义 以及对结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。

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.