Abstract PR07: Impact of race on the uterine microbiome in women with early stage endometrial cancer

Introduction: African American (AA) women suffer a higher mortality from endometrial cancer (EC) than non-Hispanic white (NHW) women. Potential biological causes for this disparity in AA women include a higher risk of more lethal histologic/molecular subtypes and greater rates of obesity. We hypothesize that another biological factor driving his racial disparity is the uterine microbiome. Thus, we evaluated the microbiota of human ECs and assessed for variations by race. Methods: Banked tumor specimens of post-menopausal patients undergoing hysterectomy for early stage endometrioid ECs were identified. Tumors were analyzed from AA and NHW women and stratified as obese (BMI≥30kg/m2) or non-obese (BMI<30kg/m2). The microbiota of the human ECs were characterized by bacterial 16S rRNA high throughput sequencing, and data was analyzed using MicrobiomeAnalyst. The microbial component of endometrioid ECs in The Cancer Genome Atlas (TCGA) database was also assessed. Results: 95 EC specimens were evaluated. Of these, 23 were from AA (24%) and 72 from NHW (76%). When analyzed by race and obesity status, we observed significant differences in EC microbiota composition. Microbial diversity was increased (p<0.001), and abundance of Firmicutes (p=0.014) and OD1 (p=0.006) were higher ECs in obese vs non-obese NHW women. When comparing ECs from obese AA vs obese NHW women, microbial diversity was increased (p<0.001), and Firmicutes, Cyanobacteria and OD1 phyla abundance was higher in the tumors from AA vs NHW women (p<0.001). Genus level abundance of Dietzia (p<0.001) and Geobacillus (p<0.001) were the top bacteria found to be lower in tumors of obese AA vs obese NHW women. Similarly, analysis of the endometrioid ECs in the TCGA database found that microbial diversity was higher in ECs from AA versus NHW women. When comparing early stage ECs from obese AA (N=11) versus obese NHW (N=115) women, 5 bacteria distinguished these two groups, with higher abundance of Lactobacillus acidophilus in AA tumors being the most striking difference. Confirming the 16S analysis, Dietzia and Geobacillus were also observed to be associated with NHW tumors, though at lower significance. Conclusion: Microbial diversity was higher in the ECs from AA versus NHW women as seen in both our institutional and TCGA dataset. Distinct microbiota profiles were found between ECs of obese AA versus obese NHW women. Better understanding of the inter-relationship of obesity and race on the EC microbiota may provide critical insight into the disparate clinical outcomes between AA and NHW women with EC.

Citation Format: Gabrielle M. Hawkins, Amber N. McCoy, Andrew Olshan, Russell Broaddus, Wendy R. Brewster, Jeffrey Roach, Temitope Keku, Victoria L. Bae-Jump. Impact of race on the uterine microbiome in women with early stage endometrial cancer [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PR07.