Abstract 3626: Deoxycytidine kinase (dCK) gene expression patterns and racial disparities: Findings from the Multiethnic Cohort study

Abstract Background: Significant disparities exist in pancreatic cancer outcomes across different racial and ethnic groups, with African Americans experiencing disproportionately higher incidence and mortality rates than other ethnic groups. The genetic underpinnings of these disparities, particularly concerning drug metabolism and treatment response, remain poorly understood. Deoxycytidine Kinase (dCK) plays a crucial role in activating nucleoside analogs for pancreatic cancer treatment. Our study aim was to characterize dCK expression patterns across different racial/ethnic groups and evaluate the association between genetic variations in dCK and survival outcomes. Methods: Germline genetic variation was analyzed on a subset of 756 cases in the Multiethnic Cohort (MEC) study. Incident pancreatic cancer cases were identified using SEER state cancer registries. Samples were genotyped across various arrays and imputed to the 1000 genomes reference panel using the Minimac4 algorithm. Imputed data was filtered to SNPs and short indels within the dCK gene coding region. Genetically determined dCK gene expression was estimated using imputed data. Associations between genetic variation and mortality among cases were estimated using Cox proportional hazards regression. Results: Sample characteristics are shown in Table 1 Table 1. Sample Characteristics: (N =756) Race/Ethnicity African-American Japanese-American Latino Native Hawaiian White Cases (n) 129 266 152 76 133 Females (%) 60.5% 59.4% 45.4% 55.3% 47.4% Deaths 122 238 136 67 127 Pancreatic Cancer Deaths 101 207 112 59 111 Person-Months Total 1253 3778 1921 1201 2488 Mean Age at Dx (years) 79.4 79.0 78.4 75.8 77.0 Mean Survival (months) 9.7 14.2 12.6 15.8 18.7 Median Survival (months) 4.1 4.9 5.2 5.5 5.0 . Nine variants from the dCK gene with an imputation quality score of R2 > 0.8 across all samples were highly correlated within each self-reported ethnic group—the highest correlation was among African Americans. There was no association between any variants and pancreatic cancer survival nor interactions between dCK variants dosage and chemotherapy treatment on mortality rate. Conclusions: To further evaluate the potential influence of the variants on survival and mortality, we are testing the protein levels using Immunohistochemistry (IHC) staining and Western blot. Citation Format: Saunjoo Yoon, Sherise Rogers, David Bogumil, Edward Agyare, Renee Reams, Mariana Stern, Seth Ablordeppey, Diana J. Wilke, Bo Han. Deoxycytidine kinase (dCK) gene expression patterns and racial disparities: Findings from the Multiethnic Cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3626.