ABSTRACT Objectives: To investigate the effect of individual-level, neighborhood, and environmental variables on uterine fibroid (UF) prevalence in a Chicago-based cohort. Methods: Data from the Chicago Multiethnic Prevention and Surveillance Study (COMPASS) were analyzed. Individual-level variables were obtained from questionnaires, neighborhood variables from the Chicago Health Atlas, and environmental variables from NASA satellite ambient air exposure levels. The Shapiro-Wilks test, logistic regression models, and Spearman’s correlations were used to evaluate the association of variables to UF diagnosis. Results: We analyzed 602 participants (mean age: 50.3±12.3) who responded to a question about UF diagnosis. More Black than White participants had a UF diagnosis (OR, 1.32; 95% CI, 0.62–2.79). We observed non-significant trends between individual-level and neighborhood variables and UF diagnosis. Ambient air pollutants, PM2.5 and DSLPM were protective against UF diagnosis (OR 0.20, CI: 0.04–0.97: OR 0.33, CI: 0.13–0.87). Conclusions: Associations observed within a sample in a specific geographic area may not be generalizable and must be interpreted cautiously.

Bromodomain (BRD)-containing proteins are involved in many biological processes, most notably epigenetic regulation of transcription, and BRD protein dysfunction has been linked to many diseases, including tumorigenesis. However, the role of BRD proteins in the pathogenesis of uterine fibroids (UFs) is entirely unknown. The present study aimed to determine the expression pattern of BRD9 protein in UFs and matching myometrium and further assess the impact of BRD9 inhibitors on UF phenotype and epigenetic/epitranscriptomic changes. Our studies demonstrated that the levels of BRD9 were significantly upregulated in UFs compared to matched myometrium, suggesting that the aberrant BRD protein expression may contribute to the pathogenesis of UFs. We then evaluated the potential roles of BRD9 using its specific inhibitor I-BRD9. Targeted inhibition of BRD9 suppressed the UF tumorigenesis with increased apoptosis and cell cycle arrest, decreased cell proliferation, and extracellular matrix deposition in UF cells. The latter is the key hallmark of UFs. Unbiased transcriptomic profiling coupled with downstream bioinformatics analysis further and extensively demonstrated that targeted inhibition of BRD9 impacted the cell cycle- and ECM-related biological pathways, reprogrammed the UF cell epigenome and epitranscriptome, and altered miRNA-mediated gene regulation in UFs. Taken together, our data support the critical role of BRD9 in UF cells and the strong interconnection between BRD9 and other pathways controlling the UF progression. Targeted inhibition of BRD proteins might provide a non-hormonal treatment option for this most common benign tumor in women of reproductive age.