Glutathione S-transferases as risk factors in prostate cancer.
Glutathione S-transferases are enzymes involved in the metabolism of carcinogens and in the defence against reactive oxygen species. Genetic polymorphisms have been detected in glutathione S-transferases M1, T1 and P1, and some of these polymorphisms have been associated with an increased risk of cancer. In a case-control study (153 cases and 288 controls) the effect of these genetic polymorphisms on the risk of prostate cancer was investigated. Homozygote deletion of either GSTM1 or GSTT1 was not associated with a statistically significant increased risk, odds ratio (OR) 1.3; 95% confidence intervals (CI) 0.9-1.9 and 1.3; 0.8-2.2, respectively. Deletion of both GSTM1 and GSTT1 gave a near-significant increased risk (OR 1.7; 95% CI 0.9-3.4). Two allelic variants of GSTP1 (codon 105) have been reported. This polymorphism was not linked to an increased risk (OR 0.8; 95% CI 0.5-1.1). Smokers that lack either GSTM1 or GSTT1 activity had a slightly higher risk of prostatic cancer than smokers expressing the genes, OR 1.4 (95% CI 0.6-3.3) and 1.6 (0.6-3.9), respectively. Our results show that differences in enzymes involved in the metabolism of carcinogens slightly modify prostate cancer risk, especially in people exposed to carcinogens that are detoxified by these enzymes.
Autrup
J L
JL
Department of Environmental Medicine, University of Aarhus, Denmark.
Thomassen
L H
LH
Olsen
J H
JH
Wolf
H
H
Autrup
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002273:Carcinogens / Q000009:adverse effects / Q000378:metabolism; D016022:Case-Control Studies; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics*; D018570:Risk Assessment; D012907:Smoking / Q000009:adverse effects
D002273:Carcinogens; D005982:Glutathione Transferase