Polymorphism of glutathione S-transferase T1, M1 and P1 genes in a Shanghai population: patients with occupational or non-occupational bladder cancer

Abstract

Objective: Glutathione S-transferases are involved in the conjugation of xenobiotics. To explore whether GSTs polymorphisms are involved in the development of occupational or non-occupational bladder cancer, polymorphism frequencies of GSTT1, M1 and P1 were investigated in a normal population, which had been settled in a rural area in Shanghai suburb for at least 5 generations as well as in a group of patients with benzidine exposure related occupational bladder cancer in Shanghai dyestuff industry and a group of patients with non-occupational bladder cancer.

Methods: PCR based procedures were performed in the study populations to confirm the genotypes of GSTT1, M1 and P1.

Results: The polymorphisms at locus of GSTP1-A1578G in the normal population differed significantly from those in Caucasians or African Americans. All the subjects genotyped so far (n = 118) bore only homogenous wild genotype (C2293/C2293) at GSTP1-C2293T locus. This locus seemed to be a monomorphic in Shanghai population. No significant difference in GSTT1 and GSTM1 polymorphic form frequencies could be confirmed among three groups of subjects. An overrepresentation of GSTP1 AG or GG genotype corresponding a less stable and less effective isozyme protein was detected in patients with benzidine related occupational bladder cancer, compared with that in the normal population though a statistical significance was not yet reached (P = 0.09, OR = 1.96, 95% CI 0.89-4.32).

Conclusion: This study suggests that GSTM1 or GSTT1 homozygous deficiency genotypes and their combination do not have a clear impact on bladder cancer incidence in a Shanghai population. It seems that GSTP1 polymorphism is not associated with non-occupational bladder cancer. GSTP1 AG or GG genotype has a higher frequency in the patients with benzidine related occupational bladder cancer, and further work is needed to confirm if GSTP1 AG or GG genotype plays a role in the development of occupational bladder cancer.