Abstract 4205: Pan-cancer molecular study of disparities among African Americans

Abstract

Abstract Objective: Several factors have been proposed to contribute to racial disparities in gynecologic cancers, however there are no comprehensive studies that have investigated inherent molecular features that may be racially unique. Our objective was to perform a pan-cancer clinical and molecular analysis of African-Americans (AA) and European American (EA) patients. Methods: We performed cross-platform analyses utilizing cancer registry and molecular databases [Surveillance, Epidemiology and End Results (SEER) and The Cancer Genome Atlas (TCGA)] to evaluate differences in AA vs EA patients. To characterize genetic ancestry we utilized the recently established The Cancer Genetic Ancestry Atlas (TCGAA). We further evaluated epigenetic modifications through non-coding RNA expression in these tumors. Results: A total of 2,045,500 patients (87.5% EA, 12.5% AA) with 64 primary tumor types were evaluated using SEER to evaluate clinical outcome differences. Compared to white race, AA race had higher rate of death in 45 cancer types (HR>1.0, CI 1.00-5.23). 19 cancer types were then identified to have the largest differences in overall survival (HR>1.2). Utilizing TCGA, we analyzed molecular data of 7028 tumors (88.9% EA, 10.9% AA) having miRSeq data and genetic ancestry data. We identified differentially expressed miRNA’s in five cancer types: breast invasive (300 miRs, p<0.068, FDR<0.1), renal cell (408 miRs, p<0.205, FDR<0.1), prostate (102 miRs, p<2.68e-01, FDR<0.1), thyroid (63 miRs, p<1.28e-.02, FDR<0.1), and uterine corpus endometrial (177 miRs, p<8.18e-02, FDR<0.1) carcinomas. Differentially expressed miRs among all cancer types were associated with canonical pathways of cancer drug resistance by drug efflux, altered T- cell function, and regulation of epithelial-mesenchymal transition using Ingenuity Pathway Analysis (IPA) software. We identified miR-130, miR-180, miR-146, and miR-8 as commonly dysregulated miRs in these cancer types which may represent a molecular signature unique to African Americans. Conclusions: Our results identify molecular and genetic features unique to African Americans that may contribute to worse survival outcomes. While the cause of cancer disparities is multifactorial, a focus on molecular signatures unique to AA may identify actionable molecular abnormalities. Note: This abstract was not presented at the meeting. Citation Format: Olivia D. Lara, Ying Wang, Wei Hu, Lin Zhang, Alejandro Rauh-Hain, Anil Sood. Pan-cancer molecular study of disparities among African Americans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4205.