Interaction of serum microRNAs and serum folate with the susceptibility to pancreatic cancer

Objectives: The aim of this study was to investigate whether 6 candidate serum miRNAs and their interactions with serum folate level were associated with the risk for pancreatic cancer (PC). Method: A hospital-based case-control study including 74 incident PC cases and 74 controls was conducted. Serum folate and miRNAs were determined by radioimmunoassay and real-time quantitative polymerase chain reaction, respectively. Cell lines AsPC-1 and PANC-1 were used for in vitro study. Results: MiR-16 was elevated (P = 0.030-0.043) and miR-103 was reduced (P = 0.018-0.020) in PC after adjustment for age, sex, and smoking; however, after additional adjustment for folate, only miR-103 was significantly different between cases and controls (P = 0.010). After converting the relative expression of miRNAs into binary variables and adjusting for age, sex, smoking, and folate, the subjects with low miR-103 or low miR-601 were observed to have a higher risk for PC, with odds ratios of 2.33 (95% confidence interval, 1.06-5.10) and 2.37 (95% confidence interval, 1.07-5.26), respectively. Multifactor dimensionality reduction analysis showed a significant interaction for miR-16, folate, and smoking (cross-validation consistency, 10/10; mean testing accuracy, 0.696; P = 0.013). Interaction between miR-16 and folate was also verified in the AsPC-1 cells. Conclusion: Serum miR-103; miR-601; and interactions among serum miR-16, folate, and smoking are associated with PC.