The Glutathione S-Transferase-μ and -θ Genotypes in the Etiology of Prostate Cancer: Genotype-Environment Interactions with Smoking

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 9; no. 12; p. 1329
• Main Authors: Kelada, S N, Kardia, S L, Walker, A H, Wein, A J, Malkowicz, S B, Rebbeck, T R
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 01-12-2000
• Subjects: Adult; Aged; Aged, 80 and over; Case-Control Studies; Confidence Intervals; European Continental Ancestry Group; Genotype; Glutathione Transferase - genetics; Humans; Male; Middle Aged; Odds Ratio; Prostatic Neoplasms - enzymology; Prostatic Neoplasms - ethnology; Prostatic Neoplasms - genetics; Risk Assessment; Smoking - adverse effects
• ISSN: 1055-9965; 1538-7755

It
has been reported that individuals who express GSTT1 ,
the gene coding for the θ 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 μ
( GSTM1 ) and θ ( 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× 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.