Abstract 2145: Genetic ancestry associations with pancreatic cancer mutational profiles from a diverse 9,274-patient real-world cohort

Abstract Pancreatic cancer is an aggressive malignancy associated with racial/ethnic disparities. Notably, Black patients have a higher incidence and mortality compared to their White counterparts. However, low representation of Black and Hispanic patients in cancer genomics studies hampers our understanding of genomic factors contributing to differential outcomes. Furthermore, comparisons between racial groups fail to capture differences in genomic ancestry. We studied the associations between genetic ancestry and race/ethnicity categories with mutational profiles, using a large, diverse real-world pancreatic cancer cohort. We analyzed 9, 274 de-identified pancreatic cancer patients (8, 483 with ductal adenocarcinoma, PDAC) who underwent tumor profiling with the Tempus xT 648-gene assay. We used 654 ancestry-informative markers to estimate continental ancestry for five regions: Africa (AFR), Americas (AMR), East Asia (EAS), Europe (EUR), and South Asia (SAS). We imputed Asian (ASN, n=431), Hispanic/Latino/Native American (HLN, n=593), Non-Hispanic Black (NHB, n=875) and Non-Hispanic White (NHW, n=7, 309) categories from genetic ancestry using a previously published machine learning method. Associations between either race/ethnicity categories or ancestry proportions and somatic variants (copy number alterations or CNAs, small nonsynonymous, OncoKB L1/2 however, despite the relatively large cohort size, these results are modest, suggesting there is not a large somatic mutation component contributing to differences in pancreatic cancer outcomes by ancestry. Citation Format: Brooke Rhead, Vignesh Vudatha, Yannick Pouliot, Edward Williamns, Andrea N. Riner, Francisco M. De La Vega, Jose Trevino. Genetic ancestry associations with pancreatic cancer mutational profiles from a diverse 9, 274-patient real-world cohort abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 2145.