Risk of pancreatic cancer in patients with vitamin D deficiency: a retrospective cohort study

Vitamin D deficiency (VDD) is highly prevalent worldwide; however, its association with pancreatic cancer risk remains inconclusive, and prior evidence has included a substantial proportion of case-control studies. This retrospective cohort study used the TriNetX Global Collaborative Network to identify adults (age ≥ 40 years) with at least two serum 25-hydroxyvitamin D measurements between 2010 and 2023. The VDD (<20 ng/ml) and control (≥30 ng/ml) cohorts were matched in a 1:1 ratio using propensity scores. A 2-year landmark period was applied. The primary outcome was incident pancreatic cancer within 10 years. Secondary outcomes included acute and chronic pancreatitis. After matching, 316 681 patients remained in each cohort. VDD was associated with a higher risk of pancreatic cancer (hazard ratio: 1.53, 95% confidence interval: 1.30-1.80, P  < 0.001), acute pancreatitis (hazard ratio: 2.03, P  < 0.001), and chronic pancreatitis (hazard ratio: 2.28, P  < 0.001). The negative control outcome (appendicitis) showed no significant difference (hazard ratio: 1.04, P  = 0.252), whereas healthcare visits used to assess detection bias were lower in the VDD group (hazard ratio: 0.88, P  < 0.001). Results remained consistent across all sensitivity models. No significant interaction was observed according to sex or age. Severe VDD (<10 ng/ml) demonstrated a stronger association with pancreatic cancer (hazard ratio: 2.25, P  < 0.001), supporting an exposure-gradient pattern. VDD was associated with higher subsequent risks of pancreatic cancer and pancreatitis, with stronger associations at lower vitamin D levels. These observational findings require prospective confirmation.