PATH-44. RACE INFLUENCES PATIENT SURVIVAL IN GLIOMA AND ASSOCIATES WITH GENETIC MARKERS OF RETINOIC ACID METABOLISM Free

African Americans (AA) have a significantly decreased incidence of glioma compared to Caucasians. However, it is not known whether the molecular biology of gliomas in AA patients fundamentally differ from those occurring in Caucasians. This study aims to investigate racial differences in clinical outcome and molecular patterns among glioma patients.

Clinical information and molecular profiles (including gene expression array, non-silent somatic mutation, DNA methylation and protein expression) were obtained from The Cancer Genome Atlas (TCGA) for both lower-grade glioma (LGG) and glioblastoma (GBM). Electronic clinical information was collected for all glioma patients treated at Northwestern University between 2006 and 2016. For clinical data, LGG and GBM were analyzed together and then separately. Molecular files were examined in GBM patients only.

931 Caucasians and 64 AA glioma patients from TCGA were analyzed. AA with Karnofsky Performance Score (KPS) ≥80 have significantly lower risk of death than similar Caucasian GBM patients (HR [95%CI] = 0.47[0.23, 0.98], P=0.0444, C index=0.68). Therefore, we further compared gene expression profiles between AA GBM patients and Caucasians with KPS≥80. Extrapolation of genes significantly associated with increased AA patient survival revealed a set of 13 genes with a possible role in this association, including elevated expression of genes previously identified as increased in AA breast and colon cancer patients (e.g. CRYBB2). Furthermore, gene set enrichment analysis revealed retinoic acid metabolism as a pathway significantly upregulated in AA GBM patients who survive longer than Caucasians (Z-score=-2.10, Adjusted P-value=0.0449).

African Americans have prolonged survival with glioma which is influenced by initial KPS score. Genes previously associated with both racial disparities in cancer, and pathways associated with RA metabolism, may play important roles in AA gliomas. More work is needed to better understand the reasons for racial disparities in glioma frequency and outcomes.