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 thoug ht to engage in the transport of steroid hormones. A case-control study was conducted to determine the association of the GSTP1, GSTM1 and GSTT1 polym orphisms and prostate-cancer risk. The study population consisted of 166 pa tients 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 a nd 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, caus ing an isoleucine-to-valine change. The GSTP1*C allele has an additional tr ansition 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 G STP1 variant alleles (GSTP1*B/*B, GSTP1*B/*C and GSTP1*C/*C) was significan tly 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 sig nificant 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 t he 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, ( C) 2001 Wiley-Liss, Inc.