Abstract C053: Differences in hallmark gene sets in the Molecular Signatures Database between tumors from African American and White patients
Authors: Abo Muthana Al , George Daniel J. , Patierno Steven R. , Freedman Jennifer A. 
Published: January 2023

Abstract
To improve cancer outcomes, it is of critical importance to understand biological differences in tumors that ultimately accompany progression to a lethal phenotype. Compared to Whites (Ws), African Americans (AAs) suffer from higher mortality rates for some cancer types, such as prostate and breast cancer. The etiology for these cancer disparities includes an array of attributes related to societal, social, lifestyle, environmental, access and individual, ancestry-related differences. A combination of these etiologies can lead to differences in cancer biology and, therefore, differences in mortality. Differential regulation of various cancer-related pathways in tumor cells can contribute to differential mortality and morbidity outcomes, and influence cancer response to treatment. Therefore, we performed pathway analysis using publicly available gene expression datasets to compare the variation in established cancer-related pathways between tumors from AA and W patients. Molecular Signatures Database (MSigDB) is a widely used database to perform gene enrichment analysis in cancer biology. Using The Cancer Genome Atlas (TCGA) datasets from 18 tumor types and the Gene Set Variation Analysis (GSVA) method, we interrogated MSigDB hallmark gene sets between tumors from AAs and Ws. By comparing the gene set variations in tumors between AAs and Ws, we identified gene sets exhibiting significant (|∆ Z-score| &gt; 2 and p &lt; 0.05) variation by race. For example, our analysis revealed that the variation of 1) MYC targets increases in breast, colon, and uterine cancer from AAs compared to Ws, 2) G2M checkpoint and E2F targets increase in breast and uterine cancer from AAs compared to Ws, and 3) interferon gamma and alpha response and allograft rejection increase in renal clear cell carcinoma from AAs compared to Ws. We also performed survival analysis to identify the MSigDB hallmark gene sets whose variation scores exhibit differential association with overall survival among AA and W patients. Among the gene sets associated differentially by race with overall survival are MYC targets in breast cancer and PI3K AKT MTOR signaling in colon cancer; with variation exhibiting an association with higher overall survival among AA patients compared with W patients. Thus, our analysis reveals how the widely accepted MSigDB hallmark gene sets differ between tumors from AAs and Ws and differentially associate with survival among AA and W patients. The majority of published studies reporting pathways relevant to cancer biology have been based on data from W patients. Therefore, evaluation of hallmark gene sets in cancers from diverse patients has important implications for understanding cancer biology and developing precision medicine interventions.
Citation Format: Muthana Al Abo, Daniel J. George, Steven R. Patierno, Jennifer A. Freedman. Differences in hallmark gene sets in the Molecular Signatures Database between tumors from African American and White patients [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C053.