Experiences of Discrimination, Dysbiosis, and Racial Disparities in Ovarian Cancer

卵巢癌中的歧视、生态失调和种族差异的经历

• 批准号: 10371537
• 负责人: April Deveaux
• 金额: $ 12.29万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-24 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10371537
• 关键词: 16S ribosomal RNA sequencing; Address; Advanced Development; Anti-Inflammatory Agents; Basic Science; Bioinformatics; Biological; Biometry; Black race; Cancer Etiology; Cancer Patient; Carcinoma; Cardiovascular Diseases; Chronic; Clinical; Communities; Data; Data Analyses; Data Collection; Data Reporting; Diabetes Mellitus; Diagnosis; Dimensions; Disadvantaged; Disparity; Drug usage; Environmental Risk Factor; Funding; Future; Geographic Factor; Grant; Guidelines; Health; Health Services Accessibility; High-Risk Cancer; Histology; Incidence; Infection; Inflammation; Intervention; Investigation; Link; Malignant Female Reproductive System Neoplasm; Malignant neoplasm of ovary; Measures; Mediating; Mental Depression; Molecular Epidemiology; Newly Diagnosed; Non-Steroidal Anti-Inflammatory Agents; Obesity; Outcome; Ovarian; Pathway interactions; Patient Self-Report; Pharmaceutical Preparations; PhenX Toolkit; Play; Psychosocial Stress; Public Health; Publishing; Recommendation; Research; Risk; Risk Factors; Sampling; Screening for Ovarian Cancer; Secondary to; Serous; Social Interaction; Socioeconomic Factors; Stage at Diagnosis; Survival Rate; Swab; Testing; Therapeutic; Therapeutic Intervention; Training; Treatment/Psychosocial Effects; United States; United States National Institutes of Health; Vagina; Woman; access disparities; acute stress; advanced disease; beta diversity; black women; cancer epidemiology; cancer health disparity; cancer initiation; cancer risk; cancer survival; cohort; disparity reduction; dysbiosis; epidemiology study; experience; follow-up; health care availability; high risk; microbial; microbial community; microbiome; mortality; mortality risk; perceived discrimination; racial difference; racial discrimination; racial disparity; reproductive tract; social; social determinants; social health determinants; socioeconomics; survival disparity; tumor progression; tumorigenesis; vaginal microbiome

Abstract In 2020, over 21,000 women were diagnosed with ovarian cancer (OC). While there have been significant therapeutic advances, effective screening for OC remains elusive. Women are more likely to present with an advanced disease stage, contributing to the dismal five-year survival rate of 48%. Mortality is disproportionately higher among Black women. Evidence has shown a multi-dimensional contribution to this disparity and, while there has been extensive investigation into socioeconomic and environmental determinants, biological contribution to the survival disparity is understudied. Because cancer disparities are multifactorial, it is imperative to study the mechanisms through which social determinants impact biological risk factors that influence advanced-stage OC. Experiences of discrimination (EOD) are more prevalent among Black women and have been associated with chronic inflammation, a risk factor for advanced-stage OC. The more aggressive subtypes of OC, including high-grade serous carcinoma (HGSC), arise from high in the reproductive tract. Inflammation that occurs in this region may be the direct result of changes in the vaginal microbiome that increase pH and promote ascending infection. Therefore, a potential pathway by which EOD may influence development of advanced-stage OC is through dysregulation of the vaginal microbiome, a phenomenon known as vaginal dysbiosis. The central thesis of this study is that psychosocial stress secondary to EOD contributes to advanced-stage OC via vaginal dysbiosis. The proposed study will collect vaginal microbial samples from Black and White women with OC and characterize the microbial community using 16S rRNA sequencing. Subsequently, we propose to conduct an in-depth association study evaluating the relationships between EOD, vaginal dysbiosis, OC stage, and survival. The associated R01-funded ORCHiD study will provide extensive information on measures of acute stress, socioeconomic and environmental factors as well as OC stage at diagnosis, course of treatment, and survival follow-up. Findings from this study will direct future analysis of the compounded social and biological effect of psychosocial stress on OC etiology and survival. The results of this study are essential to understanding the interaction of social and biological mechanisms in OC disparity. Findings will inform future studies testing clinical interventions, for example, the use of anti-inflammatory medications, as a potential strategy to mitigate disparities in advanced-stage OC.

抽象的 2020 年，超过 21,000 名女性被诊断患有卵巢癌 (OC)。虽然已经出现了重大 随着治疗的进展，有效筛查 OC 仍然难以实现。女性更有可能呈现出 疾病已进入晚期，五年生存率仅为 48%。死亡率是 黑人女性的比例更高。证据表明对此有多方面的贡献 差异，虽然对社会经济和环境进行了广泛的调查 决定因素，生物学对生存差异的贡献尚未得到充分研究。因为癌症差异是 社会决定因素影响生物风险的机制是多因素的研究当务之急 影响晚期 OC 的因素。歧视经历 (EOD) 在以下群体中更为普遍 黑人女性与慢性炎症有关，慢性炎症是晚期 OC 的危险因素。这 更具侵袭性的 OC 亚型，包括高级别浆液性癌 (HGSC)，源自高级别浆液性癌 生殖道。该区域发生的炎症可能是阴道变化的直接结果 增加 pH 值并促进上行感染的微生物组。因此，EOD 的一个潜在途径 可能通过阴道微生物群失调影响晚期 OC 的发展， 这种现象称为阴道菌群失调。本研究的中心论点是心理社会压力是继发性的 EOD 通过阴道菌群失调导致晚期 OC。拟议的研究将收集阴道 来自患有 OC 的黑人和白人女性的微生物样本，并使用 16S 表征微生物群落 rRNA 测序。随后，我们建议进行深入的关联研究，评估 EOD、阴道生态失调、OC 阶段和生存之间的关系。相关的 R01 资助的 ORCHiD 研究将提供有关急性压力、社会经济和环境措施的广泛信息 因素以及诊断时的 OC 分期、治疗过程和生存随访。这项研究的结果 将指导未来分析社会心理压力对 OC 病因的复合社会和生物学影响 和生存。这项研究的结果对于理解社会和生物的相互作用至关重要 OC 差异的机制。研究结果将为未来测试临床干预措施的研究提供信息，例如 使用抗炎药物作为缓解晚期 OC 差异的潜在策略。