Translational Research Program in Colorectal Cancer Disparities

结直肠癌差异的转化研究计划

• 批准号: 10466935
• 负责人: Christopher I Li
• 金额: $ 108.13万
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10466935
• 关键词: Address; African American; African American population; 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; Hispanic; Hispanic Populations; Immune; Incidence; Indolent; Infrastructure; Institution; Intervention; Knowledge; Laboratories; Latino; Latino Population; 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; multi-racial; novel; novel therapeutic intervention; 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）发生率和死亡率的差异是可观的，并继续持续存在 美国。这些差异在阿拉斯加本地和非洲人中特别明显 美国人口。阿拉斯加的土著人在CRC的发病率和死亡率最高 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。但是，我们对这些差异的生物基础的理解， 特别是因为它们与死亡率有关，这是有限的。我们所知的三个主要差距是：1。 了解结直肠肿瘤的分子和微生物特征的差异和相似性 根据种族/民族，2。我们从不同种族/族裔群体中识别患者的能力，他们的风险较高 CRC死亡率，谁可以从更频繁的监视和/或其他治疗方式中受益？ 3。发现和验证与CRC死亡风险有关的新型生物学特征 充当潜在的治疗靶标。考虑到CRC的独特流行病学和病因 种族/民族人群，我们假设在不同的不同的生物学差异中存在重要的生物学差异 种族/种族，这些差异将具有临床实用性，以区分懒惰 与致命的CRC，并告知新型治疗策略的发展。解决这些差距可能 直接减少持续的CRC差异。 我们关于结直肠癌差异（TRPCD）的翻译研究计划是专门的 通过新的合作和利用现有临床和 来自不同患者人群的流行病学数据和肿瘤生物测量。该程序将包括数据 来自840名CRC患者的生物测量，来自阿拉斯加本地人，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。构建所需的基础架构 通过开发行政核心，支持高度竞争性的P50孢子提案 生物测量和病理核心；和2。提高我们进行转化癌差异的能力 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例患者肿瘤进行转录组分析，以鉴定新的肿瘤 基于组织/种族的致命CRC预测指标。完整项目2将研究肠道微生物组 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 总体死亡率和种族/种族。这两个项目都有可能直接影响所描述的差距 以上关于确定临床上可行的种族/种族差异，改善了 具有致命CRC的风险的患者，发现与服务不足的种族/种族特别相关的新目标 人群。调查结果将告知干预措施，我们旨在在计划的P50孢子应用中进行测试。