Glutathione S-transferase gene polymorphisms (GSTM1, GSTT1, GSTP1) and prostate cancer: a case-control study in Tehran, Iran

Abstract

We evaluated the relationship between polymorphisms in the glutathione S-transferases (GSTs) GSTM1, GSTT1 and GSTP1 genes and prostate cancer (PCa). PCR-restriction fragment length polymorphism assay was used to genotype the GSTM1, GSTT1, and GSTP1 polymorphisms in 168 PCa cases and 336 frequency matched controls. The GSTM1 null, and GSTT1 null genotypes were associated with an increased odds ratio (OR) for PCa (OR=3.28, 95% confidence interval (CI): 2.47-5.64; P=0.005, and OR=3.21, 95% CI: 2.52-5.64; P=0.005, respectively) (Pcorrected=0.0062). The frequency of GSTP1 Val/Val genotype was 14.3% in cases compared with 2.4% in controls, this polymorphism thus being associated with a significantly increased risk of PCa (OR=3.72, 95% CI: 1.67-5.65; P=0.002). The risk associated with the concurrent absence of both of the genes (OR=4.8, 95% CI: 2.34-6.78) was greater than the product of risk in men with either null (OR=1.52, 95% CI: 0.82-2.31) genotype combinations (P=0.001, Pcorrected=0.0045). The combination of GSTP1 Ile/Val or Val/Val polymorphism with the GSTT1 null and GSTM1 null type resulted in an OR of 6.21 (95% CI: 4.83-16.87) (P=0.0001, Pcorrected=0.0062). A higher frequency of the GSTM1 null genotype and GSTT1 null genotype was observed in patients with Gleason score >7, with an OR for GSTM1 null 4.67 (95% CI: 3.64-7.62; P=0.001) and with an OR for GSTT1 null 3.62 (95% CI: 2.31-5.74; P=0.004). The results obtained demonstrated that simultaneous presence of three potentially risk alleles (GSTM1 null, GSTT1 null and GSTP1 Val) lead to a significant OR increase for PCa.