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.
Luscombe
Christopher J
CJ
Department of Urology, North Staffordshire Hospital, Stoke-on-Trent, Staffordshire, UK.
French
Michael E
ME
Liu
Samson
S
Saxby
Mark F
MF
Farrell
William E
WE
Jones
Peter W
PW
Fryer
Anthony A
AA
Strange
Richard C
RC
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000726:Androgen Antagonists / Q000494:pharmacology*; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D016896:Treatment Outcome
D000726:Androgen Antagonists; D007527:Isoenzymes; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase