Glutathione S-transferase and epoxide hydrolase activity in human leukocytes in relation to risk of lung cancer and other smoking-related cancers.
BACKGROUND
There is considerable interindividual variation in the activity of enzymes which metabolize polycyclic aromatic hydrocarbon constituents of tobacco smoke. Low activity of enzymes which detoxify carcinogenic polycyclic aromatic hydrocarbon metabolites may be associated with increased susceptibility to cancers etiologically related to cigarette smoking.


OBJECTIVE
We conducted a population-based, case-control study to determine whether patients with cancers related to smoking had lower activity of detoxifying isoenzymes of glutathione S-transferase (GST) and epoxide hydrolase (EH) than control subjects.


METHODS
Enzyme activities were measured in leukocytes from 113 King County (Washington) residents diagnosed during 1987 with one of three smoking-related cancers (lung, oropharynx/oral cavity, or bladder), 50 King County residents with cancers believed unrelated to smoking (prostate cancer or non-Hodgkin's lymphoma), and 120 persons selected at random from the King County population. Enzyme activity measurements were made for leukocyte cytosolic GST toward transstilbene oxide (TSO), 1-chloro-2,4-dinitrobenzene, and benzo[a]pyrene-4,5-oxide (BaPO), and for microsomal EH toward BaPO.


RESULTS
Overall, the distribution of activity levels of GST toward TSO and BaPO did not differ in case patients with smoking-related cancer compared with control subjects. The activities of GST toward 1-chloro-2,4-dinitrobenzene and of EH toward BaPO were somewhat lower on average in case patients with smoking-related cancers than in control subjects, but these differences were well within the limits of chance. Among the heaviest smokers, there were proportionately fewer patients with smoking-related cancers than control subjects with intermediate or high GST activity toward TSO (odds ratio = 0.6), but this difference was also plausibly due to chance (95% confidence interval = 0.3-1.1).


CONCLUSIONS
While the findings of this study are compatible with a moderate protective effect of high or intermediate enzyme activity among persons heavily exposed to tobacco, as suggested by an earlier report, the data are by no means conclusive.
Heckbert
S R
SR
Department of Epidemiology, University of Washington, Seattle 98195.
Weiss
N S
NS
Hornung
S K
SK
Eaton
D L
DL
Motulsky
A G
AG
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004851:Epoxide Hydrolases / Q000097:blood*; D005260:Female; D005982:Glutathione Transferase / Q000097:blood*; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D008175:Lung Neoplasms / Q000201:enzymology / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000201:enzymology* / Q000209:etiology; D012907:Smoking / Q000009:adverse effects*
D005982:Glutathione Transferase; D004851:Epoxide Hydrolases