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.
