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.

摘要