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: 10299030
• 负责人: Shaneda Warren Andersen
• 金额: $ 68.4万
• 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/10299030
• 关键词: Accounting; African American; African race; Age; Age of Onset; Anatomy; Aspirin; BRAF gene; Bioinformatics; Biological; Cancer Biology; Cancer Etiology; Cancer Prognosis; Cessation of life; Characteristics; Clinical; Clinical Research; Cohort Studies; Colorectal Cancer; Communities; Complex; Consensus; Data; Data Sources; Diabetes Mellitus; Diagnosis; Disease; 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 Profiling; Mutation; Natural History; Not Hispanic or Latino; Outcome; Participant; Pathologic; Pattern; Play; Population; Poverty; Precision Health; Prevalence; Prognostic Factor; Prognostic Marker; Property; Race; Randomized Controlled Trials; Research; Resources; Role; 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; base; 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; 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