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

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.

摘要 此应用程序将提供候选人，佩雷斯博士，与必要的职业发展和研究 这些经验推动了她作为独立分子癌症流行病学家的职业生涯。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， 分子和环境危险因素对癌症病因学和预后的独立和联合作用， 特别强调这些因素如何影响健康差距。卵巢上皮癌（EOC）是 美国和非洲裔美国人（AA）妇女中最致命的妇科恶性肿瘤的发病率要低得多。 与欧洲血统（EA）的女性相比，预后。这种存活的促成因素 差异是相对未知的，在这方面的研究是在其起步阶段，由于数量少的AA 现有EOC流行病学研究中的女性。考虑到慢性炎症和 EOC的病因和预后，再加上观察到的不同种族炎症生物标志物的差异，我们 这表明炎症的差异可能是AA女性EOC生存差距的原因。拟议 研究将利用两个现有的基于人群的病例对照研究，非洲裔美国人癌症 流行病学研究（AACES）和北卡罗来纳州卵巢癌研究（NCOCS），以评估 全身和局部炎症的独立和联合作用对肿瘤微环境的影响 AA女性EOC预后以及这些炎症生物标志物的差异是否有助于 平等机会委员会的种族生存差异白细胞类型和分布将用作系统性 和局部炎症。循环白细胞将从诊断时的全血细胞计数中获得 和诊断后获得的外周血样品。将从外周血中推断白细胞比例 血液DNA甲基化数据（Illumina MethylationEPIC BeadChip）。 为了测量局部炎症，我们将使用免疫组织化学来获得肿瘤浸润的计数。 淋巴细胞（FOXP 3，CD 3，CD 8）和嗜中性粒细胞（CD 66 b），并测量Klintrup 评分，肿瘤和每种白细胞类型内总体炎症的一般标志物。最后我们 将评估是否与炎症相关的暴露（例如，肥胖，止痛药使用，生殖器体 粉末暴露）导致全身和/或局部炎症，以及这些生物标志物是否 炎症相关暴露与EOC生存之间关系的介质。为了实现 根据拟议的研究目标，佩雷斯博士将获得癌症表观遗传学，分子生物学和生物学方面的额外知识。 生物学和生物信息学通过她的培训和职业发展活动，以及指导 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EOC生存率低的促成因素，并可能对 我们的目标过于远大，即要减少平机会现时种族生存的差距。