Molecular Differences in Pancreatic Ductal Adenocarcinomas from Black versus White Patients.

Abstract: Pancreatic cancer is the third leading cause of cancer-related death in the United States. Black or African American patients have a higher incidence of pancreatic cancer compared with other racial groups. It is unclear whether distinct molecular mechanisms are involved in the development of pancreatic cancer in different racial groups. To identify tumor molecular features that are distinctly associated with race in Black or African American and White patients with pancreatic ductal adenocarcinoma (the main subtype of pancreatic cancer), we analyzed deidentified patient records, including tumor sequencing data and expression of PD-L1, from the Tempus multimodal database. Patients with a primary diagnosis of pancreatic ductal adenocarcinoma and who received molecular testing between November 2017 and March 2023 were included in analyses. Among 4,249 patients analyzed in this study, 452 (10.6%) were Black or African American, and 3,797 (89.4%) were White. Black patients had a higher prevalence of TP53 mutations compared with White patients (P < 0.001). KRASG12R mutations occurred more frequently in female patients in the Black versus White group (P = 0.007). Compared with White patients, Black patients had a higher tumor mutational burden (P < 0.001) and PD-L1 overexpression (P = 0.047). In a separate analysis of recent clinical trials testing immunotherapies for pancreatic cancer, we found that Black patients and other minorities were underrepresented in most trials. These findings suggest race-associated molecular differences in tumors that may impact patient responses to immunotherapies. Our study also supports the importance of improving patient diversity in clinical trials on pancreatic cancer treatments.

Significance: By analyzing the records of patients with pancreatic cancer in the Tempus multimodal database, we identified genomic mutations and PD-L1 overexpression occurred more frequently in Black patients compared with their White counterparts. These molecular features may contribute to racial disparities in pancreatic cancer.