Abstract

Abstract Background: Marked racial disparity in ovarian cancer persists, even in equal-healthcare settings or after adjusting for social determinants of health, with disproportionately poor survival for Black women. This suggests an important role for biological factors. One such factor, the vaginal microbiome, is known to differ by race and to contribute to inflammation, but its potential role in ovarian cancer disparities remains poorly characterized. In this cross-sectional study, we examined whether vaginal fluid metabolites differ by race among patients with ovarian cancer, are associated with systemic inflammation, and if associations differ by race. Method: We recruited participants in a population-based setting, as part of the Ovarian Cancer Epidemiology, Healthcare Access and Disparities (ORCHiD) study, between March 2021 and September 2022. Eligible patients were of Black or White race, had a diagnosis of ovarian cancer, were aged 50 – 70 years, and provided biospecimens to ORCHiD. Overall, 36 patients were included in the study cohort, including 20 randomly selected White patients, and all 16 eligible Black patients. The main exposure variable was race, categorized into Black vs. White. We performed targeted metabolomics assays on cervicovaginal fluid. Three compound classes of metabolites were assayed for, including acylcarnitines (N=45 species), sphingomyelins (N=34), and ceramides (N=21). Five conventional metabolites were assayed for (glucose, glycerol, lactate, β-HB and total ketones). Also, we performed inflammatory assays on saliva for four cytokines (IL-1β, IL-10, TNF-α, and IL-6). Results: Seven targeted metabolites showed >2-fold change, three showed significant mean differences (at P < 0.05 but not at false discovery rate < 0.05), and two fairly distinct groups were recovered using partial least squares discriminant analysis and hierarchical clustering on metabolite concentrations. Of the 100 targeted metabolites considered, arachidonoylcarnitine (C20:4), the carnitine adduct of arachidonic acid, stood out as consistently different between Black and White. However, none of the conventional metabolites considered were significantly different by race. Approximately one-third of vaginal fluid metabolites considered and systemic inflammation biomarkers were significantly correlated, with no racial differences in correlations. Conclusion: Our findings show that vaginal fluid metabolites differed by race, with significant correlations between biomarkers of systemic inflammation and targeted metabolites. Our findings are novel and suggest that biological pathways involving mitochondrial dysfunction and sphingolipid metabolism may be relevant to ovarian cancer disparities. Future large-scale investigations are needed to verify these findings and examine their specific biological implication in the context of ovarian cancer disparity. Citation Format: Oyomoare L. Osazuwa-Peters, April Deveaux, Michael J. Muehlbauer, Olga Ilkayeva, James R. Bain, Temitope Keku, Andrew Berchuck, Bin Huang, Kevin Ward, Margaret G. Kuliszewski, Tomi Akinyemiju. Racial differences in vaginal fluid metabolites and associations with systemic inflammation markers among ovarian cancer patients [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B071.

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