Impact of molecular features on outcome in African American or Black women with type 1 endometrial cancer.

Abstract

5597 Background: Among women with endometrial cancer (EC), African American or Black (AAoB) population share a disproportionate burden of cancer deaths. Previous research exploring genetic and molecular explanations revealed White (W) women with EC are more likely to have mutations in PTEN, while AAoB women have higher rates of mutations in p53. However, these studies did not stratify EC by subtype, which occur at different rates among racial groups. Here, we aim to focus on molecular differences between racial groups, specifically in Type 1 EC (T1EC). Methods: Molecular data from TCGA Uterine Corpus Endometrial Carcinoma datasets on cBioPortal was used. Cancer type was filtered to Uterine Endometrioid Carcinoma Type 1 and separated by race. A total of 711 cases were analyzed for gene alterations, expression versus copy number variations, survival curves, and OncoPrints; significant findings and differences between racial groups were noted. The Surveillance, Epidemiology, and End Results (SEER) database was used to access the frequency, rate, and survival of AAoB and W with EC. Results: The genes analyzed on cBioPortal (575 W, 136 AAoB) depicted a similar alteration rate between the two groups, except for the most altered gene, PTEN (66% altered in W, 38% in AAoB). W women with a PTEN and PIK3CA alterations had significantly increased 5-year survival periods (P-value = 1.573e-3), while these alterations had no effect survival in AAoB. Six of the ten most altered genes between the two subgroups, and 6 of the 17 most actionable genes, were statistically significant for W but not for AAoB. SEER analyses depicted a frequency of 51,677 W and 3,915 AAoB, with a rate of 5.7% and 3.9%, respectively. The observed survival was 96.1% after 1 year and 85.6% after 5 years for W, compared to 92.8% after 1 year and 76.9% after 5 years for AAoB. Conclusions: Based on 5 years of data, overall survival (OS) rates among W women with T1EC are better than AAoB. PTEN mutation confers a survival advantage in W but not in AAoB, indicating that in AAoB, PTEN may play a different role or other factors may override the PTEN advantage. Additional analyses revealed non-remarkable findings, suggesting that molecular factors play a minor role in T1EC disparities or that a larger AAoB sample size is necessary. A better understanding of the downstream signaling pathways of common mutations in T1EC is necessary to further elucidate factors that contribute to racial disparities in T1EC. [Table: see text]