Abstract PO-201: African ancestry predicts serous and copy number high endometrial cancer

Abstract

Abstract Introduction: Endometrial cancer (EC) is the leading gynecologic malignancy in the United States. Histologic classification is binary, with type I, low-grade tumors being exclusively endometrioid and type II, high-grade tumors inclusive of aggressive histologies like serous carcinoma. Molecular classification defines EC as POLE ultra-mutated, microsatellite instability (MSI), copy number low (CNL) and copy number high (CNH). Relative to White women, Black women have a higher risk of serous/CNH EC with worse overall survival. We aimed to understand whether self-identified race and genetic ancestry are associated with the probability of developing serous/CNH tumors among women diagnosed with EC. Methods: We reviewed tumor genomic data from The Cancer Genome Atlas (TCGA) and The Cancer Genetic Ancestry Atlas (TCGAA) under the project Uterine Corpus Endometrial Carcinoma. We merged both datasets matching the Patient ID and extracted age of diagnosis, histology, molecular classification, self-identified race, genomically-assigned race by EIGENSTRAT, and percentage of African, European, Asian, and Native American ancestry. We used chi-square or one-way ANOVA to test for associations to Serous/CNH diagnosis. Controlling for age, we used multivariate logistic regression to determine the odds of diagnosis with serous or CNH EC. Results: We identified 568 women with EC, including 115 (20%) self-identified Black, 417 (73%) White, and 23 (4%) Asian. Significant differences in mean age at diagnosis (p<0.01), self-identified race (p<0.01), and genomically-assigned race (p<0.01) were present between women with endometrioid and serous histologies. Self-identified race and genomically-assigned race were both significantly associated with molecular subtype of cancer (p<0.01). A greater percentage of African Ancestry was seen in CNH vs CNL (27% vs 11%, p<0.01) and CNH vs MSI (27% vs 15%, p<0.001). In logistic regression, self-identified Black women had higher probability of diagnosis with serous EC (OR=2.129, CI [1.273–3.561], p<0.01) and CNH tumors (OR=2.846, CI [1.759–4.604], p<0.001) compared to self-identified White women. Relative to women characterized as European American (≥48% European Ancestry), African Americans (≥35% African ancestry) had greater odds of serous EC diagnosis (OR=2.289, CI [1.376–3.806], p<0.01) and CNH molecular type (OR=2.839 CI [1.760–4.579], p<0.01). For every 1% increase in African ancestry there was 1% increase in the probability of diagnosis with serous EC (CI [1.004–1.017], p<0.01) and 1.4% increase on the likelihood of diagnosis with CNH EC (CI [1.008–1.020], p<0.01), with this percentage increasing directly proportional. Conclusion: Our findings suggest that African ancestry is associated with an increased odds for both high-grade EC histology and molecular EC classification. Self-identified race and genomically-assigned race demonstrate similar associations with aggressive disease. Further characterization of the molecular drivers of EC, with consideration of environmental factors and how they may impact risk, is warranted. Citation Format: Alex P. Sanchez-Covarrubias, Angel D. Tabuyo-Martin, Caiden J. Walter, Alexandra Diaz, Sophia H.L. George, Matthew P. Schlumbrecht. African ancestry predicts serous and copy number high endometrial cancer [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-201.