Association between single nucleotide polymorphisms in the promoter of cyclooxygenase COX-2 gene and hereditary susceptibility to pancreatic cancer

Abstract

To evaluate the effects of -1290A > G, -1195G > A and -765G > C single nucleotide polymorphisms (SNPs) in the promoter of cyclooxygenase (COX)-2 gene on the risk of pathogenesis of pancreatic cancer. Peripheral blood samples were collected from 283 patients with pancreatic cancer and 566 normal controls. Questionnaire survey was conducted to understand the demographic data and status of smoking and smoking cessation of the subjects. Polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotypes of the gene fragments containing the 3 SNP sites in the promoter regions of the COX-2 gene. Statistical tests were performed to analyze the relations among different factors and the risk of pancreatic cancer. Three SNPs, -1290A > G, -1195G > A, and -765G > C were identified. A case-control analysis revealed 1.75-fold (95% CI = 1.16-2.64) and 2.53-fold (95% CI = 1.43-4.47) excesses of risks of developing pancreatic cancer for the -1195AA and -765CG genotype carriers respectively compared with the non-carriers. Compared with A(-1290)-G(-1195)-G(-765) containing haplotype, greater risks of developing pancreatic cancer were observed for A(-1290)-A(-1195)-G(-765), (OR = 1.26, 95%, CI = 1.02-1.56) and G(-1290)-A(-1195)-C(-765) (OR = 5.54, 95% CI = 1.79-17.16) containing haplotypes. There were interactions between the -765CG or -1195AA genotype and smoking in the risk of developing pancreatic cancer. The SNP of -1195A > G and -765G > C in the COX -2 promoter may play an important role in mediating hereditary susceptibility to developing pancreatic cancer.