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 使用很大一部分的医疗资源。 GI癌，结直肠癌（CRC）和 食管癌（EAC）占大多数与癌症相关的死亡，两者均可以预防 筛查和监视。当前的筛选测试是次优的，并且取得了可变的成功。 CRC筛查测试的主要目标是鉴定高级管状和锯齿状腺瘤，这是 高风险成为CRC以及早期CRC。 CRC的风险是可变的，有些人正在 由于CRC的家庭历史，遗传性癌症综合征或腺瘤的个人历史，因此处于高风险。 高风险人被置于积极的结肠镜检查计划中，低风险的人是 进行最小的监视计划。不幸的是，我们目前用于识别高和低CRC的系统 风险是次优的，导致监视和可预防的间隔CRC。更好的风险标记 需要CRC来防止间隔CRC并提高CRC筛选的总体效率。 类似于CRC，EAC源自食管的癌前状况叫做Barretts 食道（BE），这是食道的专门肠道化生，也是最高风险因素 EAC。它存在于美国5％的人口中。通过连续的组织学步骤进展到EAC 低年级发育不良（LGD），高级发育不良（HGD）和EAC。筛选和监视be 建议使用系列上层内窥镜检查，这在预防死亡方面有争议 来自EAC。这部分是因为与CRC一样，患者的EAC风险可变，并被置于高位。 风险和低风险筛查计划。但是，当前用于分配风险的系统不准确，并且 当前的筛选测试很昂贵。更具成本效益和准确的EAC和HGD筛选/监视 需要测定和准确的风险生物标志物。 我们建议开发一个集成到EDRN联盟的EDRN BCC，并通过 EDRN内外的合作将开发有效的GI癌症筛查生物标志物。我们建议 识别，验证和开发CRC和EAC的准确CLIA符合CLIA的风险生物标志物，以便 在当前筛选方案下防止EAC和CRC错过。此外，准确的风险分层 CRC和EAC的患者将减少当前CRC和EAC预防计划的财务影响。我们 还建议识别和验证HGD和早期阶段的准确CLIA符合CLIA的早期检测标记 可用于廉价，非镜像监视测试的EAC。