Translational Research Program in Colorectal Cancer Disparities

结直肠癌差异的转化研究计划

• 批准号: 10601404
• 负责人: Christopher I Li
• 金额: $ 70.31万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10601404
• 关键词: Translational; Research; Program; Colorectal; Cancer

Overall Summary/Abstract Disparities in colorectal cancer (CRC) incidence and mortality are appreciable and continue to persist in the United States. These disparities are particularly pronounced among the Alaska Native and African American populations. Alaska Native people have among the highest incidence and mortality rates of CRC in the world. The etiology of CRC is multi-dimensional and is influenced by diet, lifestyle factors, medical history, gut microbiome and genetics. However, our understanding of the biological bases for these disparities, particularly as they pertain to mortality, is limited. Three primary gaps in our knowledge are: 1. Our understanding of differences and similarities in the molecular and microbial characteristics of colorectal tumors by race/ethnicity, 2. Our ability to identify patients from different racial/ethnic groups who have elevated risks of CRC mortality and who could benefit from more frequent surveillance and/or additional treatment modalities; and 3. Discovery and validation of novel biological characteristics related to risk of CRC mortality that can serve as potential therapeutic targets. Given the distinct epidemiology and etiologies of CRC across racial/ethnic populations, we hypothesize that important biological differences are present across different races/ethnicities and that these differences will have clinical utility with respect to both distinguishing indolent vs. lethal CRC and informing the development of novel therapeutic strategies. Addressing these gaps could directly reduce persistent CRC disparities. Our Translational Research Program on Colorectal Cancer Disparities (TRPCD) is specifically developed to address these gaps through new collaborations and leveraging existing clinical and epidemiological data and tumor biospecimens from diverse patient populations. This program will include data and biospecimens from 840 CRC patients with equal numbers coming from Alaska Natives, African Americans, Hispanics/Latinos and non-Hispanic whites. Our two primary goals are: 1. Build the infrastructure needed to support a highly competitive P50 SPORE proposal through the development of an Administrative Core and Biospecimen and Pathology Core; and 2. Advance our capacity to conduct translational cancer disparities research through executing two high-quality Full Projects and establishing a robust Developmental Research Program. Full Project 1 will conduct transcriptomic analyses on the 840 patient tumors to identify novel tumor- tissue based predictors of lethal CRC by race/ethnicity. Full Project 2 will study the gut microbiome in the same 840 patient tumors and assess the impact of the gut microbiome on the tumor microenvironment and CRC mortality overall and by race/ethnicity. Both Projects have the potential to directly impact the gaps described above with respect to identifying clinically actionable racial/ethnic differences, improving the identification of patients at risk of lethal CRC, and discovering novel targets of particular relevance to underserved racial/ethnic populations. Findings will inform interventions that we aim to test in our planned P50 SPORE application.

摘要/Abstract 结直肠癌（CRC）发病率和死亡率的差异是明显的，并继续存在， 美国的这些差异在阿拉斯加土著人和非洲人中尤为明显。 美国人口。阿拉斯加原住民是CRC发病率和死亡率最高的人群之一， 世界CRC的病因是多方面的，受饮食、生活方式因素、病史、 肠道微生物组和遗传学。然而，我们对这些差异的生物学基础的理解， 特别是与死亡率有关的信息是有限的。我们知识上的三个主要差距是：1。我们 了解结直肠肿瘤的分子和微生物特征的差异和相似性 种族/民族2。我们能够识别来自不同种族/族裔群体的风险升高的患者， CRC死亡率和谁可以受益于更频繁的监测和/或额外的治疗方式; 和3.发现和验证与CRC死亡风险相关的新生物学特征， 作为潜在的治疗靶点。鉴于不同地区CRC的流行病学和病因学不同， 种族/民族人群，我们假设重要的生物学差异存在于不同的种族/民族人群中， 种族/民族，这些差异将在区分惰性和非惰性两方面具有临床实用性。 vs.致命的CRC和通知新的治疗策略的发展。弥补这些差距可以 直接减少持续的CRC差异。 我们的结直肠癌差异转化研究计划（TRPCD）特别是 通过新的合作和利用现有的临床和 流行病学数据和来自不同患者群体的肿瘤生物标本。该计划将包括数据 和来自840名CRC患者的生物标本，这些患者来自阿拉斯加原住民，非洲裔美国人， 西班牙裔/拉丁裔和非西班牙裔白人。我们的两个主要目标是：1。建立所需的基础设施， 通过开发管理核心，支持极具竞争力的P50 SPORE提案， 生物标本和病理学核心;以及2.提高我们进行转化癌症差异的能力 通过执行两个高质量的完整项目和建立一个强大的发展研究研究 程序.完整的项目1将对840名患者的肿瘤进行转录组学分析，以确定新的肿瘤- 根据人种/种族分类的致死性CRC的基于组织的预测因子。完整的项目2将研究肠道微生物组在相同的 840例患者肿瘤，并评估肠道微生物组对肿瘤微环境和CRC的影响 总体死亡率和按种族/族裔分列的死亡率。这两个项目都有可能直接影响所述差距 上述关于识别临床上可采取行动的种族/民族差异， 有致死性CRC风险的患者，并发现与服务不足的种族/民族 人口。调查结果将为我们计划在P50 SPORE应用程序中测试的干预措施提供信息。