Experiences of Discrimination, Dysbiosis, and Racial Disparities in Ovarian Cancer

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Abstract In 2020, over 21,000 women were diagnosed with ovarian cancer (OC). While there have been significant therapeutic advances, effective screening for OC remains elusive. Women are more likely to present with an advanced disease stage, contributing to the dismal five-year survival rate of 48%. Mortality is disproportionately higher among Black women. Evidence has shown a multi-dimensional contribution to this disparity and, while there has been extensive investigation into socioeconomic and environmental determinants, biological contribution to the survival disparity is understudied. Because cancer disparities are multifactorial, it is imperative to study the mechanisms through which social determinants impact biological risk factors that influence advanced-stage OC. Experiences of discrimination (EOD) are more prevalent among Black women and have been associated with chronic inflammation, a risk factor for advanced-stage OC. The more aggressive subtypes of OC, including high-grade serous carcinoma (HGSC), arise from high in the reproductive tract. Inflammation that occurs in this region may be the direct result of changes in the vaginal microbiome that increase pH and promote ascending infection. Therefore, a potential pathway by which EOD may influence development of advanced-stage OC is through dysregulation of the vaginal microbiome, a phenomenon known as vaginal dysbiosis. The central thesis of this study is that psychosocial stress secondary to EOD contributes to advanced-stage OC via vaginal dysbiosis. The proposed study will collect vaginal microbial samples from Black and White women with OC and characterize the microbial community using 16S rRNA sequencing. Subsequently, we propose to conduct an in-depth association study evaluating the relationships between EOD, vaginal dysbiosis, OC stage, and survival. The associated R01-funded ORCHiD study will provide extensive information on measures of acute stress, socioeconomic and environmental factors as well as OC stage at diagnosis, course of treatment, and survival follow-up. Findings from this study will direct future analysis of the compounded social and biological effect of psychosocial stress on OC etiology and survival. The results of this study are essential to understanding the interaction of social and biological mechanisms in OC disparity. Findings will inform future studies testing clinical interventions, for example, the use of anti-inflammatory medications, as a potential strategy to mitigate disparities in advanced-stage OC.