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

用于优化结肠癌和食道癌风险预测和早期检测的生物标志物

• 批准号: 10677825
• 负责人: William Mallory Grady
• 金额: $ 100.92万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-05 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10677825
• 关键词: Affect; Age; Age Years; Barrett Esophagus; Biological Assay; Biological Markers; CLIA certified; Cancer Etiology; Cancer Prevention Trial; Cessation of life; Chronic; Clinical; Collaborations; Colon; Colonoscopy; Colorectal Cancer; Cytology; Development; Devices; Dysplasia; Early Detection Research Network; Early Diagnosis; Economics; Effectiveness; Eligibility Determination; Endoscopy; Esophageal Adenocarcinoma; Esophageal Precancerous Condition; Esophagus; Familial Adenomatous Polyposis Syndrome; Family history of; Gastroesophageal reflux disease; Goals; Healthcare; Healthcare Systems; Hereditary Neoplastic Syndromes; Hereditary Nonpolyposis Colorectal Neoplasms; High grade dysplasia; Histologic; Incidence; Individual; Lesion; Malignant Neoplasms; Malignant neoplasm of esophagus; Malignant neoplasm of gastrointestinal tract; Methods; Modeling; Morbidity - disease rate; Patients; Persons; Phase; Population; Prevention; Prevention program; Program Efficiency; Progress Reports; Recommendation; Recording of previous events; Resources; Risk; Risk Factors; Risk Marker; Sampling; Screening for cancer; Serrated Adenoma; Stress; Surveillance Program; Survival Rate; System; Testing; Treatment Cost; Tubular Adenoma; United States National Institutes of Health; adenoma; clinic ready; colon cancer patients; colon cancer screening; colorectal cancer prevention; colorectal cancer risk; colorectal cancer screening; colorectal cancer treatment; cost; cost effective; detection assay; early detection biomarkers; effectiveness evaluation; esophageal cancer prevention; financial toxicity; high risk; high risk population; improved; mortality; premalignant; prevent; preventable death; progression risk; risk prediction; risk stratification; screening; screening program; social; standard of care; success; trend; virtual

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.

项目概要 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 使用很大比例的医疗资源。在胃肠道癌症中，结直肠癌 (CRC) 和 食管癌 (EAC) 占癌症相关死亡的大部分，而这两种癌症都可以通过以下方法预防： 筛查和监视。目前的筛查测试效果不佳，且成功率参差不齐。 CRC 筛查测试的一个主要目标是识别晚期管状和锯齿状腺瘤，这些腺瘤是 成为 CRC 以及早期 CRC 的高风险。结直肠癌的风险因某些人而异 由于 CRC 家族史、遗传性癌症综合征或腺瘤个人史而处于高风险。 高风险人群接受基于积极结肠镜检查的监测计划，而低风险人群则接受基于结肠镜检查的积极监测计划。 实施最低程度的监视计划。不幸的是，我们当前用于识别高和低 CRC 的系统 风险不理想，导致监测不足和过度以及可预防的间隔期 CRC。更好的风险标记 CRC 需要预防间隔性 CRC 并提高 CRC 筛查的整体有效性。 与 CRC 类似，EAC 源自称为 Barretts 的食道癌前病变 食管（BE），是食管的一种特殊肠化生，也是食管癌的最高危险因素 东非委员会。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 低度不典型增生 (LGD)、高度不典型增生 (HGD)，然后是 EAC。 BE 的筛查和监测是 建议使用连续上消化道内窥镜检查，但其预防死亡的有效性存在争议 来自 EAC。这部分是因为，与 CRC 一样，BE 患者发生 EAC 的风险各不相同，并且处于高风险状态。 风险和低风险筛查计划。然而，当前的风险分配系统并不准确，而且 目前的筛查测试价格昂贵。更具成本效益和准确的 EAC 和 HGD 筛查/监测 需要检测和准确的 BE 风险生物标志物。 我们建议开发一个 EDRN BCC，将其整合到 EDRN 联盟中，并通过 EDRN 内外的合作将开发有效的胃肠道癌症筛查生物标志物。我们建议 识别、验证和开发准确的符合 CLIA 标准的 CRC 和 EAC 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 CRC 和 EAC 患者将减少当前 CRC 和 EAC 预防计划的财务影响。我们 还建议识别和验证 HGD 和早期阶段准确的符合 CLIA 的早期检测标记 EAC 可用于廉价的非内窥镜监测测试。