Full Project 4: Molecular Pathways to Breast Cancer Mortality among African American and White Women

完整项目 4：非裔美国和白人女性乳腺癌死亡率的分子途径

• 批准号: 10004337
• 负责人: Jodie Michelle Fleming
• 金额: $ 20.06万
• 依托单位: NORTH CAROLINA CENTRAL UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10004337
• 关键词: Address; Affect; African American; Age; Bioinformatics; Biological; Biological Assay; Biology; Biometry; Breast Cancer Risk Factor; Categories; Caucasians; Clinical; Clinical Data; Cohort Studies; County; Critical Pathways; Data; Data Set; Disease; Epidemiology; Epidermal Growth Factor Receptor; Estrogen receptor negative; Estrogen receptor positive; Estrogens; Exposure to; Faculty; Faculty Recruitment; Gene Expression; Genes; Genetic Transcription; Growth Factor Gene; HGF gene; Health Sciences; Health Services; Hypoxia; Immune; Immune response; Incidence; Insulin; Insulin-Like Growth Factor I; Knowledge; Lead; Life Style; Link; Malignant Neoplasms; Mammary Neoplasms; Methodology; Methods; Minority; Mission; Modality; Molecular; Molecular Genetics; Natural Immunity; Nucleic Acids; Outcome; Participant; Pathway interactions; Patients; Population Research; Public Health; Public Health Schools; RNA; Race; Research; Research Methodology; Risk Factors; Sampling; Signal Transduction; Specialized Program of Research Excellence; Students; Survival Analysis; TP53 gene; Tamoxifen; Technology; Tissues; Translational Research; Translations; Treatment outcome; Woman; Work; adaptive immunity; anticancer research; base; biological heterogeneity; cancer health disparity; experience; genetic signature; health disparity; malignant breast neoplasm; medical schools; molecular subtypes; mortality; mortality disparity; nano-string; novel; phase 3 study; population based; response; survival prediction; survivorship; tumor; tumor heterogeneity; wound

Relative to white women, African American women have higher incidence of breast cancer before age 40 and suffer higher mortality at all ages. The Carolina Breast Cancer Study has shown that African American women are more likely to get estrogen receptor negative breast cancer and triple negative or basal-like breast cancers. Furthermore, when African American women get estrogen receptor positive breast cancers, their survivorship is lower than white women with similar disease. To better understand the biological pathways that lead to incidence mortality disparities, we will collect RNA expression data from Carolina Breast Cancer Study tumors. The Carolina Breast Cancer Study Phase 3 is a cohort study of 3000 women with breast cancer, half of which are African American women. The study was conducted in 44 counties and used population-based sampling, therefore representing catchment for the state. Detailed treatment and clinical data are available for survivorship analyses. Aim 1 will use RNA expression levels to classify participants according to tumor gene expression in crucial biologic pathways: estrogen responsiveness among luminal breast cancers, hepatocyte growth factor (HGF)-signaling among basal-like breast cancers, and immune response pathways in all subtypes. Aim 2 will link heterogeneity in tumor gene expression with exposure to breast cancer risk factors. Finally Aim 3 will link tumor gene expression with cancer outcomes. Novel data collected in this application will be combined with existing data on other important breast cancer pathways (e.g. intrinsic subtype, p53 expression subtype, EGFR signaling, hypoxia signaling, etc.) to develop a complete picture of the biology of breast cancer disparities. This project will also support an NCCU-UNC partnership by extending successful methods developed in the UNC Breast Cancer Specialized Program of Research Excellence, and transfering this knowledge to support our Lineberger-NCCU partnership. UNC Lineberger has a state-wide mission, a top ranked school of public health, and an outstanding medical school. Partnership-recruited faculty and trainees will gain expertise in research methods and technology not typically available on a campus without these health sciences strengths. Thus, while the research addresses a health disparity, the implementation of the project will also address a gap faced in conducting high impact public health and clinical/translational work at NCCU. This project will have both an important disparities and partnership endpoints.

相对于白人女性，非裔美国女性在年龄之前乳腺癌发病率更高 40岁，所有年龄段的死亡率都较高。卡罗莱纳州乳腺癌研究表明，非裔美国人 女性更容易患雌激素受体阴性乳腺癌和三阴性或基底样乳腺癌 癌症。此外，当非裔美国女性患上雌激素受体阳性乳腺癌时，她们的 存活率低于患有类似疾病的白人女性。为了更好地理解生物途径 导致发病率死亡率差异，我们将从卡罗来纳州乳腺癌研究中收集 RNA 表达数据 肿瘤。卡罗莱纳州乳腺癌研究第 3 阶段是一项针对 3000 名乳腺癌女性的队列研究，其中一半 其中有非洲裔美国女性。该研究在 44 个县进行，并使用基于人口的数据 抽样，因此代表该州的流域。详细的治疗和临床数据可用于 生存分析。目标 1 将使用 RNA 表达水平根据肿瘤基因对参与者进行分类 在关键生物学途径中的表达：腔内乳腺癌、肝细胞中的雌激素反应性 基底样乳腺癌中的生长因子（HGF）信号传导以及所有乳腺癌中的免疫反应途径 亚型。目标 2 将肿瘤基因表达的异质性与乳腺癌危险因素的暴露联系起来。 最后目标 3 将肿瘤基因表达与癌症结果联系起来。此应用程序中收集的新数据将 与其他重要乳腺癌途径的现有数据相结合（例如内在亚型、p53 表达亚型、EGFR 信号传导、缺氧信号传导等），以全面了解 乳腺癌差异。该项目还将通过扩展成功的项目来支持 NCCU-UNC 伙伴关系 北卡罗来纳大学乳腺癌专业卓越研究计划开发的方法，并转移 这些知识可以支持我们的 Lineberger-NCCU 合作伙伴关系。北卡罗来纳大学莱恩伯格分校有一个全州范围的使命， 排名第一的公共卫生学院，也是一所优秀的医学院。合作伙伴招募的教师和实习生 将获得研究方法和技术方面的专业知识，如果没有这些，校园通常无法获得这些知识 健康科学的优势。因此，虽然该研究解决了健康差距问题，但实施 该项目还将解决在开展高影响力公共卫生和临床/转化工作时面临的差距 NCCU。该项目将具有重要的差异和伙伴关系终点。