The Role of Inflammation in the Racial Disparities in Ovarian Cancer Survival

炎症在卵巢癌生存的种族差异中的作用

• 批准号: 9977134
• 负责人: Lauren Cole Peres
• 金额: $ 24.73万
• 依托单位: H. LEE MOFFITT CANCER CTR & RES INST
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9977134
• 关键词: Accounting; Address; Advisory Committees; African American; Analgesics; Anti-Inflammatory Agents; Area; Bioinformatics; Biological Markers; Blood Cell Count; Blood specimen; C-reactive protein; CD3 Antigens; CD8B1 gene; Cancer Etiology; Cancer Patient; Cancer Prognosis; Case-Control Studies; Cells; Cessation of life; Chronic; Clinical; Coupled; DNA Methylation; Data; Development; Diagnosis; Disease; Enrollment; Environmental Risk Factor; Epidemiologist; Epigenetic Process; Epithelial ovarian cancer; European; Exposure to; FOXP3 gene; Genital system; Goals; Heterogeneity; High Prevalence; Immunohistochemistry; Immunotherapy; Inflammation; Inflammatory; Interleukin-6; Joints; Knowledge; Leukocytes; Link; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of ovary; Measures; Mediating; Mediation; Mediator of activation protein; Mentors; Methods; Methylation; Modality; Molecular; Molecular Biology; North Carolina; Obesity; Patients; Pelvic Inflammatory Disease; Pharmaceutical Preparations; Physical activity; Play; Population Study; Powder dose form; Primary Neoplasm; Process; Quality of life; Questionnaires; Race; Research; Role; Source; Tobacco use; Training; Tumor-Infiltrating Lymphocytes; United States; Woman; Work; anticancer research; bead chip; cancer epidemiology; cancer immunotherapy; cancer survival; cancer type; career; career development; cell type; endometriosis; epidemiology study; experience; hazard; health disparity; improved; infancy; inflammatory marker; neutrophil; outcome forecast; ovarian neoplasm; peripheral blood; prognostic; prognostic significance; racial disparity; research and development; tumor; tumor microenvironment; Accounting; Address; Advisory Committees; African American; Analgesics; Anti-Inflammatory Agents; Area; Bioinformatics; Biological Markers; Blood Cell Count; Blood specimen; C-reactive protein; CD3 Antigens; CD8B1 gene; Cancer Etiology; Cancer Patient; Cancer Prognosis; Case-Control Studies; Cells; Cessation of life; Chronic; Clinical; Coupled; DNA Methylation; Data; Development; Diagnosis; Disease; Enrollment; Environmental Risk Factor; Epidemiologist; Epigenetic Process; Epithelial ovarian cancer; European; Exposure to; FOXP3 gene; Genital system; Goals; Heterogeneity; High Prevalence; Immunohistochemistry; Immunotherapy; Inflammation; Inflammatory; Interleukin-6; Joints; Knowledge; Leukocytes; Link; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of ovary; Measures; Mediating; Mediation; Mediator of activation protein; Mentors; Methods; Methylation; Modality; Molecular; Molecular Biology; North Carolina; Obesity; Patients; Pelvic Inflammatory Disease; Pharmaceutical Preparations; Physical activity; Play; Population Study; Powder dose form; Primary Neoplasm; Process; Quality of life; Questionnaires; Race; Research; Role; Source; Tobacco use; Training; Tumor-Infiltrating Lymphocytes; United States; Woman; Work; anticancer research; bead chip; cancer epidemiology; cancer immunotherapy; cancer survival; cancer type; career; career development; cell type; endometriosis; epidemiology study; experience; hazard; health disparity; improved; infancy; inflammatory marker; neutrophil; outcome forecast; ovarian neoplasm; peripheral blood; prognostic; prognostic significance; racial disparity; research and development; tumor; tumor microenvironment

ABSTRACT This application will provide the candidate, Dr. Peres, with the necessary career development and research experiences to propel her career as an independent molecular cancer epidemiologist. Dr. Peres’ long-term career goal is to integrate the fields of cancer epidemiology and molecular biology to disentangle the independent and joint effects of molecular and environmental risk factors on cancer etiology and prognosis, with a special emphasis on how these factors influence health disparities. Epithelial ovarian cancer (EOC) is the deadliest gynecologic malignancy in the U.S. and African American (AA) women have a much poorer prognosis in comparison to women of European ancestry (EA). The contributing factors to this survival disparity are relatively unknown, and research in this area is in its infancy due to the small numbers of AA women in existing epidemiologic studies on EOC. Given the suggested link between chronic inflammation and EOC etiology and prognosis coupled with the observed differences in biomarkers of inflammation by race, we posit that differences in inflammation may be contributing to the EOC survival gap in AA women. The proposed research will capitalize on two existing population-based case-control studies, the African American Cancer Epidemiology Study (AACES) and the North Carolina Ovarian Cancer Study (NCOCS), to evaluate how the independent and joint effects of systemic and local inflammation in the tumor microenvironment influences EOC prognosis among AA women and whether differences in these inflammatory biomarkers are contributing to the racial survival disparity in EOC. Leukocyte cell type and distribution will be used as markers of systemic and local inflammation. Circulating leukocytes will be obtained from the complete blood cell count at diagnosis and a peripheral blood sample obtained after diagnosis. Leukocyte proportions will be inferred from peripheral blood DNA methylation data (Illumina MethylationEPIC BeadChip) using cell mixture deconvolution methods. To measure local inflammation, we will use immunohistochemistry to obtain counts of tumor-infiltrating lymphocytes (FOXP3, CD3, CD8) and neutrophils (CD66b) within the primary tumor and measure the Klintrup score, a general marker of overall inflammation with the tumor and within each leukocyte cell type. Lastly, we will evaluate whether inflammatory-related exposures (e.g., obesity, analgesic medication use, genital body powder exposure) contribute to systemic and/or local inflammation, and whether these biomarkers are mediators of the relationship between inflammatory-related exposures and EOC survival. In order to achieve the proposed research objectives, Dr. Peres will obtain additional knowledge in cancer epigenetics, molecular biology and bioinformatics through her training and career development activities as well as the mentoring provided by her interdisciplinary advisory committee. The proposed research will improve our understanding of the contributing factors to poor EOC survival among AA women and will likely have a considerable impact on our over-arching goal of reducing the existing racial survival disparity in EOC.

抽象的 该申请将为候选人Peres博士提供必要的职业发展和研究 促进她作为独立分子癌流行病学家的经验。佩雷斯博士的长期 职业目标是整合癌症流行病学和分子生物学领域，以解开 分子和环境风险因素对癌症病因和预后的独立和关节影响， 特别强调这些因素如何影响健康差异。上皮卵巢癌（EOC）是 美国和非裔美国人（AA）妇女最致命的妇科恶性肿瘤的贫困 与欧洲血统妇女（EA）相比，预后。促成这种生存的因素 差异相对未知，由于AA数量少，该领域的研究处于起步阶段 现有的EOC流行病学研究中的妇女。考虑到慢性炎症与 EOC病因和预后，加上观察到的种族炎症生物标志物的差异，我们 假定炎症的差异可能会导致AA妇女的EOC生存差距。提议 研究将利用两项现有的基于人群的病例对照研究，即非裔美国人癌症 流行病学研究（AASS）和北卡罗来纳州卵巢癌研究（NCOC），以评估如何评估 全身感染和局部感染在肿瘤微环境影响中的独立和关节作用 AA妇女的EOC预后以及这些炎症生物标志物中的差异是否有助于 在EOC中的种族生存差异。白细胞细胞类型和分布将用作全身标记 和局部炎症。诊断时将从完整的血细胞计数中获得循环的白细胞 以及诊断后获得的外周血样本。白细胞比例将从外围推断 血液DNA甲基化数据（Illumina ethylationepic beadchip）使用细胞混合物反卷积方法。 为了测量局部炎症，我们将使用免疫组织化学获得肿瘤浸润的计数 淋巴细胞（FOXP3，CD3，CD8）和中性粒细胞（CD66B）在原发性肿瘤中并测量klintrup 得分，肿瘤和每种白细胞细胞类型内的总体炎症的一般标记。最后，我们 将评估炎症相关的暴露（例如肥胖，镇痛药，生殖器体）是否存在 粉末暴露）有助于系统性和/或局部炎症，以及这些生物标志物是否为 炎症相关暴露与EOC存活之间关系的介体。为了实现 拟议的研究目标，佩雷斯博士将获得有关癌症表观遗传学的更多知识，分子 生物学和生物信息学通过她的培训和职业发展活动以及心理 由她的跨学科咨询委员会提供。拟议的研究将提高我们对 AA妇女的EOC生存不良的因素，可能会对 我们降低EOC中现有的种族生存差异的整理目标。