Biomarkers for optimizing risk prediction and early detection of cancers of the colon and esophagus

项目摘要 胃肠道(GI)癌症是美国死亡率和发病率的主要原因及其治疗 使用相当大比例的医疗资源。在消化道癌症中，结直肠癌(CRC)和 食道癌(EAC)占癌症相关死亡的大部分，两者都可以通过以下方式预防 筛查和监视。目前的筛查测试不是最理想的，成功率参差不齐。 结直肠癌筛查试验的一个主要目标是识别晚期管状腺瘤和锯齿状腺瘤，这些腺瘤是 成为结直肠癌的高风险，以及早期结直肠癌。结直肠癌的风险是多种多样的，有些人 有结直肠癌家族史、遗传性癌症综合征或腺瘤个人病史的高危人群。 高危人群接受积极的结肠镜检查，而低危人群则 被置于最低限度的监视计划中。不幸的是，我们目前识别高和低CRC的系统 风险是次优的，导致监测不足和过度监测，以及可预防的间隔时间。更好的风险标记 为了预防间歇性CRC和提高CRC筛查的整体有效性，需要对CRC进行筛查。 与CRC类似，EAC由一种称为Barretts的食道癌前病变引起 食道(BE)，这是一种特殊的食管肠化生，是食管炎的最高风险因素 EAC。它存在于5%的美国人口中。BE通过连续的组织学步骤进展为EAC 低度异型增生(LGD)，高度异型增生(HGD)，然后是EAC。BE的筛查和监测 建议使用连续的上消化道内窥镜检查，这在预防死亡方面的有效性存在争议 来自EAC的。这在一定程度上是因为，与结直肠癌一样，BE患者患EAC的风险不同，而且处于高风险状态。 风险和低风险筛查计划。然而，目前的风险分配制度并不准确，而且 目前的筛查测试费用很高。更具成本效益且更准确的EAC和HGD筛查/监测 需要化验和准确的BE风险生物标志物。 我们建议开发一个EDRN BCC，它被整合到EDRN财团中，并通过 EDRN内外的合作将开发有效的GI癌症筛查生物标记物。我们建议 为CRC和EAC确定、验证和开发准确的符合CLIA标准的风险生物标志物，以便 防止在当前筛查方案下遗漏EAC和CRC。此外，准确的风险分层 结直肠癌和结直肠癌患者将减少当前结直肠癌和结直肠癌预防计划的财务影响。我们 还建议识别和验证符合CLIA标准的HGD和早期准确的早期检测标记 EAC，可用于廉价的非内窥镜监测测试。

Project Summary Gastrointestinal (GI) cancers are a major cause of mortality and morbidity in the U.S. and their treatment uses a substantial proportion of healthcare resources. Of the GI cancers, colorectal cancer (CRC) and esophageal cancer (EAC) account for a majority of the cancer related deaths, and both are preventable by screening and surveillance. The current screening tests are suboptimal and have variable success. A major goal of CRC screening tests is to identify advanced tubular and serrated adenomas, which are high-risk for becoming CRC, as well as early stage CRC. The risk for CRC is variable with some people being at high risk because of family histories of CRC, hereditary cancer syndromes, or a personal history of adenomas. High risk people are placed on aggressive colonoscopy based surveillance programs and low-risk people are placed on minimal surveillance programs. Unfortunately, our current system for identifying high and low CRC risk is suboptimal resulting in under and over surveillance and preventable interval CRCs. Better risk markers for CRC to are needed to prevent interval CRCs and improve the overall effectiveness of CRC screening. Analogous to CRC, EAC arises from a precancerous condition of the esophagus called Barretts esophagus (BE), which is a specialized intestinal metaplasia of the esophagus and the highest risk factor for EAC. It is present in 5% of the US population. BE progresses to EAC through successive histologic steps of low grade dysplasia (LGD), high grade dysplasia (HGD) and then EAC. Screening and surveillance for BE is recommended using serial upper endoscopy, which is controversial in its effectiveness for preventing deaths from EAC. This is in part because, as with CRC, BE patients have variable risk of EAC and are placed on high- risk and low-risk screening programs. However, the current system for assigning risk is not accurate and the current screening test is expensive. More cost effective and accurate EAC and HGD screening/surveillance assays and accurate BE risk biomarkers are needed. We propose to develop an EDRN BCC that is integrated into the EDRN consortium and, through collaborations within and outside the EDRN, will develop effective GI cancer screening biomarkers. We propose to identify, validate, and develop accurate CLIA compliant risk biomarkers for CRC and for EAC in order to prevent EAC and CRC missed under current screening protocols. Moreover, the accurate risk stratification of patients for CRC and EAC will reduce the financial impact of current CRC and EAC prevention programs. We also propose to identify and validate accurate CLIA compliant early detection markers for HGD and early stage EAC that can be used in an inexpensive, non-endoscopic surveillance test.