Study on the polymorphisms and promoter methylation and expression of the glutathione S-transferases P1 gene in hepatocellular carcinoma

Objective To study the relationships between hepatocellular carcinoma (HCC) and the polymorphisms,promoter methylation,and expression of glutathione S-transferases P1 gene (GST) P1 gene.Methods Using methylation-special PCR (MSP),the methylated status of CpG islands of GSTP1 gene in tumor tissues of 53 HCC and its adjacent nontumor tissues were studied.The enzyme activities of GSTP1 were evaluated by ultraviolet colormetry.And using PCR-RFLP,the genetic polymorphisms of the GSTP1 genes of 74 healthy controls and 53 HCC patients were studied.Results The diffe-rences of the frequency of GSTP1 Ile/Ile,Ile/Val and Val/Val genotypes between HCC patients and the normal controls did not reach statistical significance (X~2=0.84,v=2,P=0.656).The frequency of methyla- tion of CpG islands of GSTP1 gene was significantly higher among the HCC tumor tissues when com- pared to the corresponding nontumor tissues (X~2=19.08,P＜0.001),and significantly higher in stageⅢ-Ⅳcases when compared to the stageⅠ-Ⅱcases (X~2=4.84,P=0.028).GSTP1 enzyme activities of cytoplasm in tumor cells were lower significantly than that in the adjacent nontumor tissues (t=2.49, P=0.014),and significantly higher in stageⅠ-Ⅱcases when compared to the stageⅢ-Ⅳcases (t= 2.31,P=0.025).On the other hand,the GSTP1 enzyme activities of cytoplasm in tumor cells with methylated status of GSTP1 gene were significantly lower than that in tumor cells with unmethylation (t=3.50,P=0.001).Conclusion GSTP1 inactivation via CpG island hypermethylation may contrib- ute to the pathogenesis of HCC.