title: The glutathione S-transferase-mu and -theta genotypes in the etiology of prostate cancer: genotype-environment interactions with smoking.
abstract: It has been reported that individuals who express GSTT1, the gene coding for the theta class of the glutathione S-transferases (GSTs), have an elevated risk of prostate cancer (CaP). This result is supported by studies that show glutathione conjugation of some xenobiotics by the GSTs can produce mutagenic intermediates. However, the potential role of environmental factors in modifying the risk of CaP conferred by GSTT1 is not known. We investigated whether there was an interaction between smoking and the non-deleted genotypes of the mu (GSTM1) and theta (GSTT1) GST genes using a clinic-based study of 276 CaP cases and 499 controls. We observed no main effect of smoking (odds ratio, 0.95; confidence interval, 0.69-1.29) or GSTM1 (odds ratio, 1.00; confidence interval, 0.73-1.36) with CaP, but did observe a statistically significant main effect of GSTT1 with CaP (odds ratio, 1.61; confidence interval, 1.14-2.28) as reported previously. No interaction between smoking and GSTM1 was observed. A significant increase in the probability of having CaP was observed in men who were both smokers and carried a non-deleted GSTT1 genotype compared with men who had neither or only one of these risk factors (P = 0.049). Approximately 30.9% of CaP cases in this study could be attributed to the smoking x GSTT1 interaction. Whereas the mechanism of this interaction is not known, it is plausible that the metabolism of carcinogenic intermediates or the response to chronic inflammation associated with smoking may be modulated by the GSTT1 genotype and may modify CaP risk.
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor 48109, USA.
authors.forename: S N
authors.initials: SN
authors.lastname: Kelada
authors.forename: S L
authors.initials: SL
authors.lastname: Kardia
authors.forename: A H
authors.initials: AH
authors.lastname: Walker
authors.forename: A J
authors.initials: AJ
authors.lastname: Wein
authors.forename: S B
authors.initials: SB
authors.lastname: Malkowicz
authors.forename: T R
authors.initials: TR
authors.lastname: Rebbeck
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016001:Confidence Intervals; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D018570:Risk Assessment; D012907:Smoking / Q000009:adverse effects; D044465:White People
chemical_list: D005982:Glutathione Transferase