Translational Research Program in Colorectal Cancer Disparities

结直肠癌差异的转化研究计划

• 批准号: 10044047
• 负责人: Christopher I Li
• 金额: $ 120.4万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH 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/10044047
• 关键词: Address; African American; Alaska Native; Bacteria; Biologic Characteristic; Biological; Cancer Control; Characteristics; Clinical; Clinical Data; Collaborations; Colorectal Cancer; Colorectal Neoplasms; Communities; Data; Development; Diet; Disease; Ensure; Epidemiology; Ethnic Origin; Ethnic group; Etiology; Evaluation; Feedback; Fostering; Foundations; Funding; Future; Gene Expression; Genetic; Goals; Hispanics; Immune; Incidence; Indolent; Infrastructure; Institution; Intervention; Knowledge; Laboratories; Latino; Lead; Leadership; Medical History; Modality; Molecular; Monitor; Native Americans; Native-Born; Not Hispanic or Latino; Pathology; Patients; Play; Population; Primary Prevention; RNA; Race; Research; Resources; Risk; Role; Scientist; Secondary Prevention; Services; Specimen; Specimen Handling; Testing; Translational Research; Tumor Tissue; United States; Validation; Vision; Work; base; cancer health disparity; career; clinically actionable; colon cancer patients; colorectal cancer risk; community based participatory research; data management; epidemiologic data; ethnic difference; ethnic diversity; gut microbiome; high risk; improved; lifestyle factors; microbial; microbiome; mortality; novel; novel therapeutic intervention; novel therapeutics; patient population; prevent; programs; racial and ethnic; repository; therapeutic target; transcriptomics; translational research program; tumor; tumor DNA; tumor microenvironment

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.

总体摘要/摘要 结直肠癌(CRC)发病率和死亡率之间的差异是明显的，并将继续存在 美国。这些差异在阿拉斯加原住民和非洲人中尤为明显 美国人口。阿拉斯加原住民是#年结直肠癌发病率和死亡率最高的人群之一 整个世界。结直肠癌的病因是多方面的，受饮食、生活方式因素、病史、 肠道微生物群和遗传学。然而，我们对这些差异的生物学基础的理解， 特别是在与死亡率有关的情况下，这一点是有限的。我们知识中的三个主要差距是：1.我们的 认识结直肠肿瘤分子和微生物学特性的异同 通过种族/民族，2.我们识别来自不同种族/民族的患者的能力，这些患者的风险增加 CRC死亡率以及谁可以从更频繁的监测和/或其他治疗方式中受益； 以及3.发现和验证与结直肠癌死亡风险相关的新的生物学特征，这些特征可以 作为潜在的治疗靶点。考虑到世界各地结直肠癌的不同流行病学和病因 种族/民族人口，我们假设重要的生物学差异存在于不同的 种族/民族，这些差异将在区分懒惰方面具有临床实用价值 与致命性结直肠癌的对比，并为开发新的治疗策略提供信息。解决这些差距可以 直接减少长期存在的《儿童权利公约》差距。 我们的结直肠癌差异翻译研究计划(TRPCD)特别是 旨在通过新的协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。该程序将包括数据 以及来自840名同等数量的结直肠癌患者的生物标本，这些患者来自阿拉斯加原住民，非裔美国人， 拉美裔/拉美裔和非拉美裔白人。我们的两个主要目标是：1.建立所需的基础设施 通过开发管理核心和支持极具竞争力的P50孢子提案 生物医学和病理学核心；和2.提高我们进行癌症差异翻译的能力 实施两个高质量全程攻关创建强势发展研究 程序。Full Project 1将对840名患者的肿瘤进行转录分析，以确定新的肿瘤- 以组织为基础的种族/民族致死性结直肠癌预测因素。完整的项目2将研究肠道微生物群 840例肿瘤患者，评估肠道微生物群对肿瘤微环境和结直肠癌的影响 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 以上关于确定临床上可操作的种族/民族差异、改进对 有致命结直肠癌风险的患者，并发现与服务不足的种族/民族特别相关的新靶点 人口。研究结果将为我们计划在P50孢子应用中测试的干预措施提供信息。