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

摘要 相对于白人女性，非裔美国女性在年龄之前患乳腺癌的几率更高 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，非裔美国人 女性更有可能患上雌激素受体阴性的乳腺癌和三重阴性或基底样乳房 癌症。此外，当非裔美国女性患上雌激素受体阳性的乳腺癌时，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 导致发病率和死亡率差异，我们将收集卡罗莱纳州乳腺癌研究的RNA表达数据 肿瘤。卡罗莱纳乳腺癌研究第三阶段是对3000名患有乳腺癌的女性进行的队列研究，其中一半 其中包括非洲裔美国女性。这项研究是在44个县进行的，使用了基于人口的方法 采样，因此代表该州的集水区。详细的治疗和临床数据可用于 生存分析。Aim 1将使用RNA表达水平来根据肿瘤基因对参与者进行分类 关键生物学途径的表达：雌激素在腔性乳腺癌、肝细胞中的反应性 生长因子(HGF)在基底细胞样乳腺癌中的信号转导，以及ALL中的免疫反应途径 子类型。目的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，Aim 3将把肿瘤基因的表达与癌症的结果联系起来。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相结合(例如固有亚型、p53 表达亚型、EGFR信号、缺氧信号等)对…的生物学有一个完整的了解 乳腺癌的差异。该项目还将支持NCCU-UNC伙伴关系，将成功的 方法在北卡罗来纳大学乳腺癌专业计划的卓越研究，并转移 这一知识支持我们Lineberger和NCCU的合作伙伴关系。北卡罗来纳大学莱恩伯格在全州范围内有一个使命，一个顶级 公共卫生学院排名靠前，是一所优秀的医学院。伙伴关系--招聘教员和实习生 将获得研究方法和技术方面的专业知识，这是没有这些的校园通常无法获得的 健康科学的强项。因此，虽然这项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/翻译工作方面面临的差距 NCCU。这个项目将既有重要的差异，又有伙伴关系的终点。

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.