Full Project 3: Molecular Pathways to Breast Cancer Mortality among African American and White Women

摘要 相对于白色女性，非裔美国女性在年龄之前的乳腺癌发病率更高 40岁，所有年龄段的死亡率都较高。卡罗莱纳乳腺癌研究表明， 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， 癌的此外，当非裔美国妇女患上雌激素受体阳性乳腺癌时， 存活率低于患有类似疾病的白色女性。为了更好地理解 导致发病率和死亡率差异，我们将从卡罗莱纳乳腺癌研究中收集RNA表达数据 肿瘤的卡罗莱纳乳腺癌研究第3期是一项对3000名乳腺癌女性进行的队列研究，其中一半 其中包括非裔美国女性。这项研究在44个县进行， 采样，因此代表国家的流域。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 关键生物学途径中的表达：乳腺癌、肝细胞癌和乳腺癌间的雌激素反应性 基底细胞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局联系起来。在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（如内在亚型，p53 表达亚型、EGFR信号传导、缺氧信号传导等）来建立一个完整的 乳腺癌差异。该项目还将通过扩展成功的合作伙伴关系来支持NCCU-UNC的合作伙伴关系 研究卓越的乳腺癌专业计划中开发的方法， 这些知识来支持我们的Lineberger-NCCU合作伙伴关系。莱恩伯格有一个全州范围的使命，一个顶级的 排名第一的公共卫生学院和一所杰出的医学院。合作招聘的教师和实习生 将获得研究方法和技术的专业知识，而这些知识在没有这些知识的校园里通常是无法获得的。 健康科学优势。因此，虽然研究解决了健康差距，但实施 该项目还将解决在开展高影响力的公共卫生和临床/转化工作时面临的差距， NCCU。这个项目将有一个重要的差异和伙伴关系的终点。

Abstract 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.