Glutathione S-transferase GSTP1 genotypes are associated with response to androgen ablation therapy in advanced prostate cancer

We determined whether the glutathione S-transferase GSTP1 Ile105→Val105 substitution is associated with response to androgen ablation therapy in patients with advanced prostate cancer. As response may be associated with tumor grade, Gleason score, clinical T stage and presence of metastases we also determined if GSTP1 genotypes were associated with these prognostic parameters. We speculated that GSTP1 Ile105/Ile105 would be linked with good response to androgen ablation therapy and, low/moderate tumor grade, 1/2 clinical T-stage, Gleason score <6 and, no metastases. Genotype frequencies in cases and controls were not significantly different (P=0.70) indicating that allelism in GSTP1 is not associated with susceptibility. There was no association between GSTP1 (Ile105/Ile105 versus Ile105/Val105 and Val105/Val105) and grade (P=0.28, OR=0.92), Gleason score (P=0.84, OR=0.94) or metastatic state (P=0.68, OR=0.88) though the frequency of GSTP1 Ile105/Ile105 was higher in cases with stage 1/2 tumors than those with stage 3/4 tumors (P=0.03, OR=1.89). GSTP1 Val105/Val105 was also associated with response to hormone ablation therapy. Thus, the GSTP1 Ile105/Ile105 frequency was significantly higher in 86/118 patients who demonstrated a good response than in those with poor response (P=0.03, OR=2.70). We speculate that the association of GSTP1 with response results from an effect of the gene product early in carcinogenesis.