Role of obesity as a causative factor of breast cancer in women of African American ethnicity

项目摘要 乳腺癌（BC）不仅本身是一种异质性疾病，而且还具有不同的种族影响。 在预后方面，与欧洲人相比，非裔美国人（AA）血统的妇女的预后较差 美国人非洲血统女性的BC出现在更年轻的年龄，并与更先进的 与年龄匹配的EA或亚洲血统患者的乳腺癌相比， （阿萨）。几个因素，包括种族和健康因素的社会决定因素（SDOH），包括肥胖 增加了疾病性质的复杂性。这些环境压力源的长期存在， 在BC种族/民族不平等中的决定性作用。我们建议调查SDOH和生物学的交叉点， 肿瘤生物学的决定因素，通过检查肥胖和祖先相关的炎性 因素及其对肿瘤基因组和免疫学景观的影响。在这个项目中，协会 在混合的非洲BC患者中， 在亚拉巴马的黑带将被探索。我们将确定与遗传祖先相关的肿瘤差异 免疫微环境与全身性炎症和肥胖有关。为此，我们采用了 塔斯基吉全面癌症护理协议，与当地医疗保健提供者和患者合作， 使用纵向收集的数据和生物标本来开发一种基于证据的方法， 少数患者的需求。我们将通过三个不同的具体目标，利用病例对照研究， 将从广泛的以患者为中心的人群水平因素分层流向系统和基因组水平因素 来表征肿瘤和肿瘤内的异质细胞类型。这些将有助于确定不同的风险因素 它捕捉了肿瘤表型背后的社会和生物学机制。整合这些数据 将提供新的机会，以制定干预措施，在社区一级，这将有助于克服免疫 和炎症驱动/肥胖相关的BC进展

PROJECT SUMMARY Breast cancer (BC) is not only a heterogenous disease by itself but it also has a differential racial impact. Prognostically, it has an inferior outcome in women of African American (AA) descent as compared to European American. BC in women of African ancestry presents at a younger age and is associated with more advanced disease and higher mortality rates as compared to breast cancer in age-matched patients of EA or Asian ancestry (AsA). Several factors, including ethnicity and social determinants of health factors (SDOH), including obesity adds to the complexity to nature of the disease. The chronicity of these environmental stressors has played a determinate role in racial/ethnic BC inequities. We propose to investigate the intersection of SDOH and biological determinants of tumor biology by examining the convergence of obesity- and ancestry-related inflammatory factors and their consequences on tumor genomic and immunological landscapes. In this project, the association of the obesity-associated inflammatory signature for those with African ancestry in admixed-African BC patients in Black Belt Alabama will be explored. We will determine genetic ancestry-associated differences in tumor immune microenvironments linked to systemic inflammation and obesity. To do so, we have adopted the Tuskegee Total Cancer Care protocol, which partners with local health care providers and patients with the goals of using longitudinally collected data and biospecimens to develop an evidence-based approach that meets the needs of minority patients. We will work through three distinct specific aims, utilizing case-control studies, which will flow hierarchically from broad patient-centered population-level factors to systemic-and genomic-level factors to characteristics tumors and heterogeneous cell types within the tumor. These will help define distinct risk factors that capture both the social and biological mechanisms that underlie tumor phenotypes. Integration of these data will provide new opportunities to develop interventions that, on a community level, will help to overcome immune and inflammation-driven/obesity-related BC progression