Polymorphisms of glutathione-S-transferase genes (GSTP1, GSTM1 and GSTT1) and prostate-cancer risk.
Several polymorphic glutathione-S-transferase (GST) enzymes are involved in the metabolism of a number of potential prostate carcinogens and are thought to engage in the transport of steroid hormones. A case-control study was conducted to determine the association of the GSTP1, GSTM1 and GSTT1 polymorphisms and prostate-cancer risk. The study population consisted of 166 patients with previously untreated, histologically proven prostate cancer and 166 age-matched control patients with benign prostatic hyperplasia (BPH), all of them Caucasians. In the GSTP1 gene, 2 polymorphic alleles, GSTP1*B and GSTP1*C, have been described in addition to the wild-type allele, GSTP1*A. Both polymorphic GSTP1 alleles have an A-to-G transition in exon 5, causing an isoleucine-to-valine change. The GSTP1*C allele has an additional transition from C to T. For GSTM1 as well as GSTT1, the polymorphic allele is a deletion of the gene. The proportion of individuals homozygous for the GSTP1 variant alleles (GSTP1*B/*B, GSTP1*B/*C and GSTP1*C/*C) was significantly lower in prostate-cancer patients (4.8%) than in BPH controls (14.5%), and the odds ratio (OR) was 0.24 [95% confidence interval (CI) = 0.09-0.61). The heterozygous genotypes (GSTP1*A/*B and GSTP1*A/*C) were also lower in the cancer group, though this was not significant. On the contrary, no significant effect on prostate-cancer risk was detectable for either GSTM1 (OR = 0.86, 95% CI = 0.55-1.36) or GSTT1 (OR = 0.78, 95% CI = 0.43-1.42). Of the polymorphic GSTs, GSTP1 is the most interesting candidate as a biomarker for prostate-cancer risk as we found a 76% reduced risk in men homozygous for the polymorphic GSTP1 alleles compared to those with wild-type GSTP1.
Gsur
A
A
Division of Applied and Experimental Oncology, Institute of Cancer Research, University of Vienna, Borschkegasse 8a, 1090 Vienna, Austria. andrea.gsur@univie.ac.at
Haidinger
G
G
Hinteregger
S
S
Bernhofer
G
G
Schatzl
G
G
Madersbacher
S
S
Marberger
M
M
Vutuc
C
C
Micksche
M
M
D000368:Aged; D016022:Case-Control Studies; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D011470:Prostatic Hyperplasia / Q000235:genetics; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics*; D012307:Risk Factors
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human