Abstract B057: Racial disparity research in ovarian cancer: Evaluating race definition in differential gene expression

Abstract

Abstract Objective: Several studies have reported worse prognosis for Black ovarian cancer patients in comparison to non-Hispanic White patients, even after adjusting for clinical parameters, treatment and environmental factors. Self-reported race has been widely recognized as one of the biggest limitations to racial disparities research. Here we evaluated the effect of race definition in the survival outcome and differential gene expression profiling of 72 high-grade serous ovarian carcinoma patients. Methods: We isolated total RNA and genomic DNA from tumor tissue cores of 72 self-reported (SR) Black and non-Hispanic White patients with high-grade serous ovarian carcinoma. Racial genetic admixture (RGA) was performed using a custom panel of previously validated SNPs for estimation of ancestry from African, European, and Amerindian ancestry. Full-genome RNAseq library was constructed and sequenced on Illumina HiSeq instrument. Differentially expressed genes were inferred using DESeq2 software. Candidate gene sets of significantly regulated genes were used for functional and pathway enrichment analyses. Results: 72 patients were included with SR 58% (n=42) Non-Hispanic White and 42% (n=30) Black. SR black patients had mean RGA of African descent of 89.6% (range 48.3-100%), while SR white patients had mean European descent of 88.6% (range 27.5-99.7%). Survivals were similar between SR groups. However, survival differences were seen when compared by proportion of African racial genetic admixture (RGA). Regardless of SR, patients with the highest tertile of African ancestry (AA) had lower median progression-free survival than patients in the lowest AA tertile (8 vs. 23mos; p=0.003). An OS difference of 27 vs. 54mos was seen for the highest and lowest AA tertiles, respectively (p=0.02). Genetic analyses were grouped based on (a) SR vs. (b) Tertiles for African RGA vs. (c) Continuous African RGA. A total of 1,954 genes demonstrated significant up/down expression across all racial cohorts. The “Top 40” genes with the greatest 20 upregulated and 20 downregulated log-fold expression for each genetic cohort demonstrated low concordance among the 3 genetic cohorts, with sentinel genes specific to each racial cohort. Subsequent pathway analyses based on gene expression demonstrated low concordance rates among racial cohorts as well. Conclusions: Racial genetic admixture for African ancestry was more predictive of disparate progression-free survival in high-grade serous ovarian carcinoma than self-designated race. Additionally, how race was defined had significant differences in global gene expression levels and subsequent molecular pathway analyses. Collectively, these data support the incorporation of racial genetic admixture when evaluating biologic etiologies of racial disparities in cancer. Citation Format: Luciana Madeira da Silva, Dmytro Starenki, Megan Missanelli, Jennifer Young-Pierce, Jerlinda Ross, Jaroslav Slamecka, Nathaniel Jones, Jennifer Scalici, Rodney P. Rocconi. Racial disparity research in ovarian cancer: Evaluating race definition in differential gene expression [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B057.