Abstract
The vaginal microbiome differs by race and contributes to inflammation by directly producing or consuming metabolites or by indirectly inducing host immune response, but its potential contributions to ovarian cancer (OC) disparities remain unclear. In this exploratory cross-sectional study, we examine whether vaginal fluid metabolites differ by race among patients with OC, if they are associated with systemic inflammation, and if such associations differ by race. Study participants were recruited from the Ovarian Cancer Epidemiology, Healthcare Access, and Disparities Study between March 2021 and September 2022. Our study included 36 study participants with ovarian cancer who provided biospecimens; 20 randomly selected White patients and all 16 eligible Black patients, aged 50–70 years. Acylcarnitines (n = 45 species), sphingomyelins (n = 34), and ceramides (n = 21) were assayed on cervicovaginal fluid, while four cytokines (IL-1β, IL-10, TNF-α, and IL-6) were assayed on saliva. Seven metabolites showed >2-fold differences, two showed significant differences using the Wilcoxon rank-sum test (p < 0.05; False Discovery Rate > 0.05), and 30 metabolites had coefficients > ±0.1 in a Penalized Discriminant Analysis that achieved two distinct clusters by race. Arachidonoylcarnitine, the carnitine adduct of arachidonic acid, appeared to be consistently different by race. Thirty-eight vaginal fluid metabolites were significantly correlated with systemic inflammation biomarkers, irrespective of race. These findings suggest that vaginal fluid metabolites may differ by race, are linked with systemic inflammation, and hint at a potential role for mitochondrial dysfunction and sphingolipid metabolism in OC disparities. Larger studies are needed to verify these findings and further establish specific biological mechanisms that may link the vaginal microbiome with OC racial disparities.
| Original language | English |
|---|---|
| Article number | 1259 |
| Journal | Cancers |
| Volume | 16 |
| Issue number | 7 |
| DOIs | |
| State | Published - Apr 2024 |
Bibliographical note
Publisher Copyright:© 2024 by the authors.
Funding
We thank all the patients who participated in the ORCHiD study for their vital contribution in advancing the science of cancer in the United States. We also thank Lauren Wilson and Ashwini Joshi for their contributions, including data management and grammar corrections. Texas Cancer Registry (TCR), Texas Department of State Health Services; Maryland Cancer Registry (MCR), Maryland Department of Health; California Cancer Registry (CCR), California Department of Public Health; New York State Cancer Registry (NYSCR), New York State Department of Health; Kentucky Cancer Registry (KCR); Emory University Rollins School of Public Health: Department of Epidemiology. The findings and conclusions in this publication are those of the author(s) and do not necessarily represent the views of the above-mentioned cancer registries. Cancer data were used by the Maryland Cancer Registry, Center for Cancer Prevention and Control, Maryland Department of Health, with funding from the State of Maryland and the Maryland Cigarette Restitution Fund to provide assistance in patient recruitment. The collection and availability of cancer registry data is also supported by the Cooperative Agreement NU58DP006333, funded by the Centers for Disease Control and Prevention. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention or the Department of Health and Human Services. The collection of cancer incidence data used in this study was supported by the California Department of Public Health pursuant to California Health and Safety Code Section 103885; Centers for Disease Control and Prevention\u2019s (CDC) National Program of Cancer Registries, under cooperative agreement 5NU58DP006344; the National Cancer Institute\u2019s Surveillance, Epidemiology and End Results Program under contract HHSN261201800032I awarded to the University of California, San Francisco, contract HHSN261201800015I awarded to the University of South-ern California, and contract HHSN261201800009I awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the author(s) and do not necessarily reflect the opinions of the State of California, Department of Public Health, the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors. Kentucky cancer data have been provided by the Kentucky Cancer Registry, 2365 Harrods-burg Road, Lexington, KY 40504 ( www.kcr.uky.edu (accessed on 8 March 2022). Data from the Kentucky Cancer Registry is supported by the following: Cooperative Agreement #NU58DP007144 from the Centers for Disease Control and Prevention and Contract #HHSN261201800013I from the National Cancer Institute\u2019s Surveillance, Epidemiology, and End Results (SEER) Program. The ideas and opinions expressed herein are those of the author(s) and do not necessarily reflect the opinions of the National Cancer Institute, the Centers for Disease Control and Prevention or their Con-tractors and Subcontractors, and the Commonwealth of Kentucky. Texas cancer data have been provided by the Texas Cancer Registry, Cancer Epidemiology and Surveillance Branch, Texas Department of State Health Services, 1100 West 49th Street, Austin, TX 78756, USA ( www.dshs.texas.gov/tcr (accessed on 19 January 2022)). Data from the Texas Cancer Registry is supported by the following: Cooperative Agreement #1NU58DP007140 from the Centers for Disease Control and Prevention, Contract #75N91021D00011 from the National Cancer Institute\u2019s Surveillance, Epidemiology, and End Results (SEER) Program, and the Cancer Prevention and Research Institute of Texas. This work was supported in part by the Centers for Disease Control and Prevention\u2019s National Program of Cancer Registries through cooperative agreement NU58DP007218 awarded to the New York State Department of Health and by Contract 75N91018D00005 (Task Order 75N91018F00001) from the National Cancer Institute, National Institutes of Health. The collection of cancer incidence data in Georgia was supported by contract HHSN261201800003I, Task Order HHSN26100001 from the NCI and cooperative agreement 6NU58DP006352-05-01 from the CDC. This research was funded by the National Institutes of Health/National Cancer Institute (Grant Number R37CA233777; PI: TA). J.R. Bain was supported by NIH 5P30DK124723, 5R01DK117491, 1U24DK129557, and 2P30AG027816, and USDA 2020-28640-31521.
| Funders | Funder number |
|---|---|
| Kentucky Cancer Registry | |
| State of Maryland Office of the Chief Medical Examiner | |
| National Cancer Institute’s Surveillance, Epidemiology and End Results Program | |
| Maryland Department of Health | |
| U.S. Department of Agriculture | 2020-28640-31521 |
| U.S. Department of Agriculture | |
| National Childhood Cancer Registry – National Cancer Institute | 1NU58DP007140, 75N91021D00011, 6NU58DP006352-05-01, R37CA233777 |
| National Childhood Cancer Registry – National Cancer Institute | |
| Centers for Disease Control and Prevention | 5NU58DP006344 |
| Centers for Disease Control and Prevention | |
| Maryland Cigarette Restitution Fund | NU58DP006333 |
| National Institutes of Health (NIH) | 2P30AG027816, 1U24DK129557, 5R01DK117491, HHSN26100001, 5P30DK124723, HHSN261201800003I |
| National Institutes of Health (NIH) | |
| Cancer Prevention and Research Institute of Texas | 75N91018D00005, 75N91018F00001, NU58DP007218 |
| Cancer Prevention and Research Institute of Texas |
Keywords
- biological pathways
- cancer disparities
- inflammatory biomarkers
- race
- social disadvantage
- targeted metabolomics
ASJC Scopus subject areas
- Oncology
- Cancer Research
