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Polymorphisms of glutathione‐ S ‐transferase genes ( GSTP1, GSTM1 and GSTT1 ) and prostate‐cancer risk
Author(s) -
Gsur Andrea,
Haidinger Gerald,
Hinteregger Sonja,
Bernhofer Gabriele,
Schatzl Georg,
Madersbacher Stephan,
Marberger Michael,
Vutuc Christian,
Micksche Michael
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20010520)95:3<152::aid-ijc1026>3.0.co;2-s
Subject(s) - gstp1 , prostate cancer , allele , odds ratio , genotype , glutathione s transferase , medicine , biology , prostate , cancer , endocrinology , genetics , glutathione , gene , enzyme , biochemistry
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. © 2001 Wiley‐Liss, Inc.