Abstract C026: Pharmacogenetics of pancreatic ductal adenocarcinoma: A review of racial disparities

Abstract

Abstract Background Pancreatic Ductal adenocarcinoma (PDAC) is currently the third leading cause of cancer mortality and is projected to increase in incidence by 2030 in the United States. Compared to Caucasians, African Americans (AA) have a significantly increased risk for PDAC, even after adjusting for risk factors (e.g., SES, obesity and smoking), and worse survival outcomes. Somatic and germline mutations are found in 90% and 10% PDAC cases, respectively. These mutations are known to alter the incidence and therapeutic response of PDAC, and studies show significant differences in genetic expression between AA and Caucasians. Our study focused on the current understanding of genetic mutations that influence the pharmacoethnicity of FDA approved PDAC drugs. Methods For this narrative review, multiple searches were generated from the PubMed database using several variations of the following keywords: pharmacogenetics, pancreatic cancer, race, ethnicity, African, Black, toxicity, and the FDA approved drug names: Fluoropyrimidines, Topoisomerase inhibitors, Gemcitabine, Nab-Paclitaxel, Platinum agents, Pembrolizumab, PARP-inhibitors, and NTRK fusion inhibitors. Names of genes were extracted from studies with established data on pharmacogenetic-related racial disparities. Additional studies were found from the cited section. After searches for PubMed was thoroughly reviewed, the same keywords were imputed in Web of Science. The University of Alabama at Birmingham (UALCAN) database was used to verify if overall survival was significant for the expression of the genes identified in literature. Only genes that were found in the literature and UALCAN database were included. Results The following genes were identified as influencing pharmacogenetic-related disparities and then assessed for significance in overall survival using the UALCAN database: CDA, TYMS, UGT1A1, SLC and ABCB transporters, BRCA 2, PALB2, ERCC1, ERCC2, NTRK 1-3, POLA2, and CY2C8. The following genes were not significant for overall survival: CDA, UGT1A1, PALB2, ERCC1, ECCR2, NTRK 1-3. TYMS (p=0.0052), POLA2 (p=0.022), CYP2C8 (p=0.027), BRCA2 (p=0.027) genes were significant for impacting overall survival outcomes. The UALCAN database has low sample size of African Americans (n=6) therefore, significance for overall survival based on race could not be properly stratified. Conclusion In conclusion, racial differences in gene expression can influence the therapeutic response of PDAC. The UALCAN database provides overall survival for patients with PDAC, but conclusions about race could not be properly stratified due to the low sample size of African Americans. As targeted therapy advancements improve, referrals for genetic testing should also because it can direct treatment course for avoiding toxicities and improving medical precision for AA. Citation Format: Guettchina Telisnor, Esther Frimpong, Edward Agyare, John M. Allen, Sherise C. Rogers. Pharmacogenetics of pancreatic ductal adenocarcinoma: A review of racial disparities [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 C026.