Association between single nucleotide polymorphisms in promoter of COX-2 gene and hereditary susceptibility to hepatocellular carcinoma

Objective To evaluate the effects of SNPs in the promoter of COX-2 gene on the risk of developing hepatocellular carcinoma. Methods Genotypes of 270 cases of hepatocellular carci-noma and 640 control subjects were determined by polymerase chain reaction-based restriction frag-ment length polymorphism (PCR-RFLP). The samples of DNA were extracted from the peripheral blood of all subjects. All patients with hepatocellular carcinoma were diagnosed by pathological or cy-tological examination. Ors and 96% CI were calculated by logistic regression to explore the associa-tion between different genotypes or haplotypes and the risk of hepatocellular carcinoma. Results Three SNPs, -1290A＞G, -1195G＞A and -765G＞C were identified. A case-control analysis re-vealed 1.57-fold (95% CI=1.01-2.44) and 2.89-fold (95% CI=1.65-5.08) excess risks of develo-ping hepatocellular carcinoma for the -1195AA or -765CG genotype carriers compared with noncar-riers, respectively. Compared with A-1290-G-1195-G-765 containing haplotype,greater risks of develo-ping hepatocellular carcinoma were observed for A1290-A-1195-G-765 (OR= 1.27; 95% CI= 1.01 -1.60) and A-1290-A-1195-C-765(OR= 7.95; 95% CI= 1.76-36.02) containing haplotypes. A greater risk of developing hepatoeellular carcinoma was observed for A-1195and C-765 containing haplotype compared with other haplotypes, suggesting an interaction between the -1195A and -765C in the context of haplotype. Conclusion The SNP of -1195A＞G and -765G＞C in the COX-2 promoter may play an important role in mediating hereditary susceptibility to developing hepatocellular carcinoma. Key words: Carcinoma,hepatocellular; Cyclooxygenase-2; Single Nucleotide Polymorphism