Genetic Polymorphisms Of Glutatione S-Transferase P1 And Bladder Cancer Susceptibility In A Chinese Population

Background GST comprises a family of isoenzymes that play a key role in the detoxification of such exogenous substrates as xenobiotics, environmental substances, and carcinogenic compounds. GSTs catalyze the conjugation of a range of alkylating agents, including potential carcinogens and pharmacologically active compounds, to the -SH groups of the antioxidant glutathione, which renders the products more water?soluble compared with the original agents. GSTs play an important role in the protection of cells from the products of oxidative stress, as well as from several environmental carcinogens. In humans, eight distinct gene families encode soluble GSTs; among them, four are mainly expressed in human tissues: GSTA, GSTM, GSTT, and GSTP. Glutathione S-transferase P1 is an important phase II enzyme involved in the metabolism of xenobiotics and whose polymorphisms have been related to individual cancer risks. With regard to cigarette smoke, GSTP1 polymorphism has gained much attention, as GSTP1 is involved in the inactivation of carcinogens, such as benzo[a]pyrene?7,8?diol?9,10?epoxide. The objective of this study was to explore the association of GSTP1 A1578G (Ile105Val) polymorphism with susceptibility and clinicopathologic characteristics of bladder cancer in a Chinese population.Methods We investigated the distribution of GSTP1 A1578G polymorphism in 200 bladder cancer patients and in 200 age and sex-matched cancer-free controls. The polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism assay. Genotype and allele frequencies and their associations with demographic factors, smoking status, stage, grade, and histological type of bladder cancer were investigated.Results1. There was an association between smoking status and bladder cancer (odds ratio= 1.77, 95% confidence interval =1.17-2.67, P=0.007).2. Photograph of the PCR product is 176 bp. Photograph of the PCR products of the glutathione S-transferase P1 (GSTP1) gene after Alw 26 I enzyme cutting and on 4% agarose gel. Line MARKER shows the 100 bp DNA ladder, line 1 and 4 shows individuals with AA genotype (176 bp), line 2 and 5 shows AG genotype (176 bp, 91 bp, 85 bp), and line 3 shows the GG genotype (91 bp, 85 bp).3. The prevalence of GSTP1 GG genotype in cases was 22.5%, compared with 13.5% in the control group (odds ratio=1.86, 95% confidence interval=1.10-3.14, P=0.02).4. Genotype and allele frequencies were in Hardy-Weinberg equilibrium (P = 0.18).5. When stratifying by the stage, grade, and histological type of bladder cancer, we found no statistical association. Conclusions These data seem to indicate that the GSTP1 GG genotype is associated with a modest increase in the risk of bladder cancer in a Chinese population.