Racial/ethnic differences in functional metabolites among ovarian cancer patients

摘要

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.