Pancreatic cancer and diabetes: The effects of race and genes.

Abstract

627 Background: Pancreatic cancer and diabetes mellitus (DM) have been shown to be connected, but the genetic associations between the two have not been well characterized. The goal of this study was to identify racial and genomic patterns that relate the timing of DM onset with a pancreatic cancer diagnosis. Methods: Consecutive pancreatic cancer patients treated at the University of Cincinnati Cancer Center with available tumor genomic profiles were studied. Descriptive statistics for 133 genes, patient characteristics, cancer stage, treatment details, and family history were analyzed. Categorical variables were compared using the Pearson Chi-square test for contingency tables (or Fisher’s exact test when the expected frequency within any cell was less than 5 in the contingency table), and the t-test or ANOVA was used for continuous variables. For overall survival, we generated Kaplan-Meier curves by DM diagnosis, and fit univariable Cox Proportional-Hazard models for each interest variable for all patients, and multivariable Cox models, which included only significant variables. Results: Of 147 individuals with pancreatic cancer (median age 67 years, 49% female, 12% Black), 46.3% had a DM diagnosis. Of these, 62% had chronic DM, while 38% were diagnosed within one year of their pancreatic cancer diagnosis. Black individuals were more likely to have DM diagnosed (76.5% vs 41.7%, p = 0.007), and were more likely to have been diagnosed within a year of pancreatic cancer (69.2% vs 30.2%, p = 0.023), compared with White individuals. There were 15 genes found to be upregulated in those with DM and pancreatic cancer, and 11 genes found to be downregulated. RNF43 mutation was more prevalent in pancreatic cancer patients with chronic DM than those without DM (71.4% vs 32.5%, p = 0.048), although absolute number of individuals with the mutation were low. No other genomic association on the timing of DM and pancreatic cancer was found. A SMAD4 mutation was associated with a 121% increased risk of mortality (HR = 2.21, 95% CI 1.16-4.19, p=0.016). Conclusions: In a cohort of pancreatic cancer patients at a single center, Black individuals were more likely to have DM diagnosed closer to pancreatic cancer diagnosis (rather than earlier), compared with other races. No remarkable genomic association was found. This highlights that a diagnosis of diabetes may be related to inequities in healthcare, as opposed to true genomic differences, and needs to be explored in larger datasets.