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.

总体总结/摘要 结直肠癌 (CRC) 发病率和死亡率的差异相当大，并且持续存在 美国。这些差异在阿拉斯加原住民和非洲人中尤其明显 美国人口。阿拉斯加原住民是 CRC 发病率和死亡率最高的国家之一 世界。 CRC的病因是多维的，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， 特别是当它们与死亡率有关时，其作用是有限的。我们知识中的三个主要差距是： 1. 我们的知识 了解结直肠肿瘤分子和微生物特征的差异和相似之处 按种族/族裔，2. 我们有能力识别来自不同种族/族裔群体的具有较高风险的患者 结直肠癌死亡率以及谁可以从更频繁的监测和/或额外的治疗方式中受益； 3. 发现并验证与结直肠癌死亡风险相关的新生物学特征 作为潜在的治疗靶点。鉴于 CRC 不同的流行病学和病因学 种族/民族群体中，我们假设不同种族之间存在重要的生物学差异 种族/民族，这些差异对于区分惰性 与致命性结直肠癌的比较，并为新型治疗策略的开发提供信息。解决这些差距可以 直接减少持续存在的 CRC 差异。 我们的结直肠癌差异转化研究计划 (TRPCD) 专门针对 旨在通过新的合作和利用现有的临床和 来自不同患者群体的流行病学数据和肿瘤生物样本。该程序将包含数据 以及来自 840 名 CRC 患者的生物样本，其中同等数量的患者来自阿拉斯加原住民、非裔美国人、 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. 建设所需的基础设施 通过开发管理核心来支持极具竞争力的 P50 SPORE 提案 生物样本和病理学核心； 2. 提高我们转化癌症差异的能力 通过执行两个高质量的完整项目并建立强大的发展研究来进行研究 程序。完整项目 1 将对 840 名患者肿瘤进行转录组分析，以鉴定新的肿瘤 - 按种族/族裔划分的基于组织的致死性 CRC 预测因子。完整项目 2 将在相同的条件下研究肠道微生物组 840 名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/民族划分的死亡率。这两个项目都有可能直接影响所描述的差距 上述关于识别临床上可采取行动的种族/民族差异，提高对 具有致命性结直肠癌风险的患者，并发现与服务不足的种族/民族特别相关的新目标 人口。研究结果将为我们计划在 P50 SPORE 应用中测试的干预措施提供信息。