Understanding the Contribution of Colorectal Cancer Tumor Characteristics to Disparities in Colorectal Cancer Survival

了解结直肠癌肿瘤特征对结直肠癌生存差异的影响

• 批准号: 10672226
• 负责人: Shaneda Warren Andersen
• 金额: $ 48.24万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10672226
• 关键词: African American; African American population; African race; Age; Age of Onset; Anatomy; Aspirin; BRAF gene; Bioinformatics; Biological; Cancer Biology; Cancer Etiology; Cancer Prognosis; Cessation of life; Characteristics; Classification; Clinical; Clinical Research; Cohort Studies; Colorectal Cancer; Communities; Complex; Consensus; Data; Data Sources; Diabetes Mellitus; Diagnosis; Disease; Disparity; Education; Epidemiology; Foundations; Frequencies; Future; Gene Expression; Gene Expression Profiling; Genes; Genomics; Goals; Household; Income; Intervention Studies; Knowledge; Link; Malignant Neoplasms; Measures; Mesenchymal; Microsatellite Instability; Modeling; Molecular; Molecular Epidemiology; Molecular Epidemiology of Cancer; Molecular Profiling; Mutation; Natural History; Not Hispanic or Latino; Outcome; Participant; Pathologic; Pattern; Population; Poverty; Precision Health; Prevalence; Prognostic Factor; Prognostic Marker; Property; Race; Randomized, Controlled Trials; Research; Resources; Sampling; Screening for cancer; Smoking; Socioeconomic Status; Somatic Mutation; Survival Rate; The Cancer Genome Atlas; Tissue Sample; Tumor Biology; Tumor Markers; Tumor Subtype; Tumor Tissue; Woman; Women' s Health; black women; cancer health disparity; cancer survival; caucasian American; cohort; colon cancer patients; colorectal cancer screening; colorectal cancer treatment; differences in access; epidemiology study; experience; improved; innovation; insight; men; molecular subtypes; mortality; mutational status; novel; precision medicine; prognostic; racial difference; racial disparity; racial population; research study; secondary analysis; survival disparity; survival outcome; targeted treatment; transcriptome sequencing; transcriptomics; tumor; uptake

PROJECT ABSTRACT Colorectal cancer (CRC) is the second leading cause of cancer death among U.S. men and women. Racial disparities in CRC survival exist, where the CRC mortality rate for African Americans is 40% higher than the mortality rate for non-Hispanic white Americans. Evidence suggests there may be racial differences in intrinsic CRC tumor biology. We hypothesize that the molecular profile of CRC tumors is more aggressive on average for African Americans than white Americans, and that these tumor differences contribute to the racial disparity in survival. The overarching goal of the project is to define how the CRC survival disparity experienced by African Americans may be influenced by complex biologic differences in tumor characteristics, measured by molecular subtypes, driver gene status, and clinicopathologic markers. The research plan uses molecular epidemiologic and cancer biology approaches to achieve our study aims by leveraging resources from three established research studies, including CRC tumor tissue data from approximately 420 African American CRC patients and 404 non-Hispanic white CRC patients from the Southern Community Cohort Study, the Black Women’s Health Study, and The Cancer Genome Atlas (TCGA). To fulfill Aim 1, we will characterize CRC tumors from white and African American CRC patients for clinicopathologic markers (anatomic site, stage), microsatellite instability, driver gene status (BRAF, and RAS mutation status), and the recently-defined CRC consensus molecular subtypes. The proposed project will be the first study to define CRC consensus molecular subtypes in African Americans. Bioinformatics approaches will identify novel gene- expression molecular subtypes, measured using RNA-seq, to explore the possibility of detecting molecular subtypes that are more prevalent among African American tumors and that may be linked to CRC prognosis. (Aim 2). Lastly, to fulfill Aim 3, associations will be determined between the abovementioned tumor characteristics and CRC survival, and assessed for differences by race. The scientific impact of the proposed study will be to determine the biological mechanisms contributing to CRC survival disparities experienced by African Americans by uncovering the molecular attributes of the tumors themselves. The results of the study will establish the essential foundation for future interventional studies. Currently, CRC treatment is determined by a combination of molecular factors including stage and the presence of somatic mutations. Emerging CRC therapies may be guided by additional tumor factors such as tumor gene-expression or the presence of other targetable features. The existing limited knowledge of the biologic properties of African American CRCs reduces the prospect that precision medicine will be effective. The proposed study aims to provide data on African American CRC tumor molecular profiles to support subtype-specific treatments and precision health strategies to decrease mortality and reduce racial disparities.

项目摘要 结直肠癌（CRC）是美国男性和女性癌症死亡的第二大原因。种族 CRC生存的差异存在，非裔美国人的CRC死亡率比 非西班牙裔美国人的死亡率。证据表明内在的种族差异 CRC肿瘤生物学。我们假设CRC肿瘤的分子特征平均更具侵略性 对于非洲裔美国人而不是白人，这些肿瘤差异导致种族差异 在生存中。该项目的总体目标是定义CRC生存差异如何经历 非裔美国人可能受到肿瘤特征上复杂的生物学差异的影响， 通过分子亚型，驱动基因状态和临床病理学标志物测量。研究计划 使用分子流行病学和癌症生物学方法来实现我们的研究目标 来自三项既定研究的资源，包括大约420的CRC肿瘤组织数据 来自南方社区的非裔美国人CRC患者和404名非西班牙裔白人CRC患者 队列研究，黑人妇女健康研究和癌症基因组地图集（​​TCGA）。为了实现目标1，我们 将表征来自白人和非裔美国人CRC患者的CRC肿瘤的临床病理标记 （解剖部位，阶段），微卫星不稳定性，驱动基因状态（BRAF和RAS突变状态）以及 最近定义的CRC共识分子亚型。拟议的项目将是第一个定义的研究 非洲裔美国人的CRC共识分子亚型。生物信息学方法将确定新的基因 使用RNA-Seq测量的表达分子亚型，以探索检测分子的可能性 在非裔美国人肿瘤中更普遍的亚型，并且可能与CRC预后有关。 （目标2）。最后，要实现AIM 3，将在上述肿瘤之间确定关联 特征和CRC生存，并评估种族差异。拟议的科学影响 研究将是确定导致CRC生存分布的生物学机制 非洲裔美国人通过发现肿瘤本身的分子特性。研究结果 将为将来的介入研究建立基础。目前，确定CRC治疗 结合分子因素，包括分期和躯体突变的存在。新兴的CRC 疗法可以以其他肿瘤因子（例如肿瘤基因表达或其他其他肿瘤因素）为指导 可目标的功能。现有对非裔美国人CRC生物学特性的有限了解 降低了精密医学将有效的前景。拟议的研究旨在提供有关 非裔美国人CRC肿瘤分子概况，以支持亚型特异性治疗和精度健康 降低死亡率并减少种族分布的策略。