Racial/ethnic differences in functional metabolites among ovarian cancer patients

卵巢癌患者功能代谢物的种族/民族差异

• 批准号: 10531800
• 负责人: Tomi F Akinyemiju
• 金额: $ 19.65万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10531800
• 关键词: Accounting; Acids; Affect; Age; Amines; Anaerobic Bacteria; BRCA1 Mutation; Biochemical; Biological; Black race; Cancer Patient; Cessation of life; Communities; Data; Disadvantaged; Discriminant Analysis; Disease; Epidemiology; Ethnic Origin; Female; Generations; Genetic Predisposition to Disease; Genomics; Glucose; Glycerol; Goals; HIV; Health; Health Services Accessibility; Health Status; Human Microbiome; Immune; Incidence; Inflammation; Inflammatory; Integration Host Factors; Interleukin-1 beta; Interleukin-10; Interleukin-6; Investigation; Lactic acid; Lactobacillus; Least-Squares Analysis; Light; Link; Lipids; Liquid substance; Low Prevalence; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Malignant neoplasm of ovary; Mediating; Microbe; Nature; Obesity; Outcome; Ovarian; Ovulation; Parents; Patients; Pelvic Inflammatory Disease; Play; Population; Premature Birth; Production; Race; Regimen; Reporting; Reproductive Health; Research; Risk; Risk Factors; Role; Sampling; Severities; Severity of illness; Shapes; Socioeconomic Status; Source; Sphingolipids; Survival Rate; TNF gene; Talc; Testing; Therapeutic; Translating; Vagina; Woman; acylcarnitine; amino acid metabolism; antimicrobial; base; beta-Hydroxybutyrate; black women; cancer diagnosis; cancer risk; cancer survival; career; cervicovaginal; cervicovaginal microbiome; cytokine; design; diagnostic biomarker; differences in access; ethnic difference; female reproductive system; health care availability; lipid metabolism; metabolomics; microbial; microbiome; microbiome composition; mortality; racial and ethnic; racial and ethnic disparities; racial difference; racial disparity; systemic inflammatory response; therapeutically effective; tumor microenvironment; tumor progression; tumorigenesis; vaginal microbiome; vaginal microbiota

ABSTRACT Ovarian cancer is the most lethal gynecological cancer with 21,000 incident cases and 14,000 deaths projected to occur in the US in 2021. Black women have the lowest 5-year survival rates for ovarian cancer of 36% compared to 46% for White women. This marked racial disparity in ovarian cancer persists even when there is no difference in access to healthcare among races or among patients of similar socioeconomic status, thus justifying a need to probe potential underlying biological mechanisms. The vaginal microbiome is one such mechanism that may underlie population differences in ovarian cancer survival and disease severity due to its potential for creating and sustaining an inflammatory tumor micro-environment through metabolite production. Vaginal microbial communities that are Lactobacillus-poor tend to be common among Black women, and are characterized by reduced levels of antimicrobial metabolites, higher levels of inflammation- inducing lipids, and products from altered amino acid metabolism. Moreover, major contributing sources to systemic inflammation, a known risk factor for ovarian cancer, such as pelvic inflammation disorder, talc exposure, and obesity, tend to be more prevalent among Black women. Given that Lactobacillus-poor vaginal microbiomes are more common among Black women, it is important to understand whether racial differences in vaginal microbiome composition translate to functional differences that can exert effects on the tumor microenvironment and contribute to systemic inflammation. In this proposed project, we will assess differences in anti-microbial and inflammation-inducing metabolites within cervicovaginal fluid of Black vs. White ovarian cancer patients. We will also evaluate racial differences in markers of systemic inflammation and the relationship between markers of systemic inflammation and functional metabolites of vaginal microbiome. Findings from this study would inform the generation of hypotheses on specific biological mechanisms that might underlie disparities in ovarian cancer health outcomes, providing the basis for further investigation. Also, it would provide information that would shed light on the potential for certain emerging therapeutic approaches to help bridge ovarian outcome disparities for Black women.

抽象的 卵巢癌是最致命的妇科癌症，有 21,000 例发病病例和 14,000 例死亡 预计将于 2021 年在美国发生。黑人女性的卵巢癌 5 年生存率最低 白人女性的这一比例为 36%，而白人女性的比例为 46%。即使在卵巢癌发生的情况下，这种显着的种族差异仍然存在 不同种族或具有相似社会经济地位的患者在获得医疗保健方面没有差异， 从而证明有必要探索潜在的潜在生物学机制。阴道微生物群是其中之一 这种机制可能是卵巢癌生存率和疾病严重程度的人群差异的基础 其通过代谢物创造和维持炎症肿瘤微环境的潜力 生产。缺乏乳酸菌的阴道微生物群落在黑人中很常见 女性，其特点是抗菌代谢物水平降低，炎症水平较高 诱导脂质和氨基酸代谢改变的产物。此外，主要贡献来源 全身炎症，卵巢癌的已知危险因素，例如盆腔炎症、滑石粉 暴露和肥胖在黑人女性中往往更为普遍。鉴于阴道内缺乏乳酸菌 微生物组在黑人女性中更为常见，了解种族差异是否存在很重要 阴道微生物组组成转化为功能差异，可以对肿瘤产生影响 微环境并导致全身炎症。在这个拟议的项目中，我们将评估差异 黑人与白人卵巢宫颈阴道液中的抗微生物和炎症诱导代谢物 癌症患者。我们还将评估全身炎症标志物的种族差异以及 全身炎症标志物与阴道微生物功能代谢物之间的关系。 这项研究的结果将为特定生物学机制的假设的产生提供信息 可能是卵巢癌健康结果差异的根源，为进一步研究提供了基础。还， 它将提供有助于揭示某些新兴治疗方法潜力的信息 帮助缩小黑人女性卵巢结果的差异。