Elucidating racial and ethnic differences in functional effects of the vaginal microbiome in ovarian cancer

ABSTRACT. This K22 proposal aims to enhance the applicant’s prior quantitative training with a combination of formal coursework and informal guidance to transition to independence as a molecular cancer epidemiologist investigating the biological basis of health disparities in female cancers. Racial and ethnic

disparities are well documented for ovarian cancer, the deadliest gynecological cancer. Black women, compared to White women, have higher odds of late stage diagnosis, and disproportionately worse survival rates despite lower incidence. Moreover, Black and Hispanic women have experienced slower decline rates in

ovarian cancer mortality compared to White women. Social determinants of health only partially account for these disparities, suggesting that biological factors like the vaginal microbiome may play a non-trivial role. The vaginal microbiome can shape the tumor microenvironment through production of pro-carcinogenic metabolites

and reduction of antineoplastic metabolites. However, its composition varies by host factors including race and ethnicity and correlates of social disadvantage such as poverty. While racially and ethnically distinct vaginal microbiomes may have unique metabolic profiles associated with differential ovarian cancer outcomes, no

studies have evaluated this possibility. Therefore, applying the framework of Krieger’s ecosocial theory, we hypothesize that through embodiment of social disadvantage, racial and ethnic differences in the functional effects of the vaginal microbiome contribute to ovarian cancer disparities. We propose a study that will use an

untargeted metabolomics approach to compare metabolite profiles of cervicovaginal fluid from 120 patients (40 Black, 40 Hispanic, and 40 White), by race and ethnicity and by social disadvantage. To test our central hypothesis, we have set three specific aims, namely to, i) characterize racial and ethnic differences in vaginal

fluid metabolite profiles, and metabolic signatures among OC patients , ii) assess differences by social disadvantage in vaginal fluid metabolite profiles, and metabolic signatures among OC patients, at the individual and neighborhood levels, and iii) evaluate the relative importance of vaginal fluid metabolites and social

disadvantage on OC aggressiveness, and OC recurrence. Completion of the proposed K22 will enhance scientific knowledge on the role of vaginal microbiome-induced inflammation in ovarian cancer progression. This study will identify biological pathways that contribute to racial and ethnic differences in ovarian cancer

progression. This scientific knowledge will be useful for identifying metabolites that can serve as prognostic biomarkers for ovarian cancer, and designing future mechanistic studies. Moreover, at the clinical level, our study will provide evidence on how therapeutic interventions that involve modulating the vaginal microbiome

may be beneficial for specific races and ethnicities, and indicate the potential value of applying vaginal microbiome metabolite profiling in clinical settings. The proposed K22 study will provide the applicant with the necessary training, skills and resources to transition to independence as a molecular cancer epidemiologist.