© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 20, 1575-1576,
October 17, 2001
© 2001 Oxford University Press
CORRESPONDENCE |
Re: Metabolites of a Tobacco-Specific Lung Carcinogen in Nonsmoking Women Exposed to Environmental Tobacco Smoke
Affiliations of authors: N. S. Chobanyan, Diagnostic Medical Center, Yerevan, Armenia; A. K. Nersesyan, Cancer Research Center, Yerevan.
Correspondence to: Armen K. Nersesyan, Ph.D., Sc.D., Department of Genetics, State University, 1 Alex Manoukian St., Yerevan 25, Armenia. (e-mail: genetik{at}ysu.am).
The report by Anderson et al. (1) on metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK) in nonsmoking women exposed to environmental tobacco smoke is an important contribution that explains the excess risk for lung cancer in this cohort of women. But it should be noted that there is a substantial difference in the mean ages of exposed and control women (48.3 and 33.4 years, respectively). Generally, it would be better if the authors choose exposed and control subjects of the same age, because age is a modifying factor for cytochrome P450 activity (2) (CYP2D6 and/or CYP2E1, which catalyzes the activation of NNK) (3,4). Moreover, this study was restricted to women. Mean age of 48.3 years means that females included in the study were premenopausal and/or postmenopausal. However, control subjects were younger females with normal menstrual function. Investigations (5,6) showed that CYP2D6 activity varies during pregnancy and the menstrual cycle. Therefore, CYP2D6 expression may be influenced by endogenous steroid sex hormones (2). Levels of steroid sex hormones in the plasma of premenopausal and postmenopausal women differ. So we suggest that age of subjects included in the study may be the main confounding factor in this research.
There are also some minor confounding factors. The authors should take into consideration alcohol use, because alcohol consumption can cause changes in the activities or expression of various forms of cytochrome P450 involved in metabolic activation of NNK (7). Any difference in the consumption of alcohol in the two groups investigated should be noted.
The ethnicity of control and treated subjects was not the same, although this factor also plays an important role in the activity of cytochrome P450 (6). Caucasian women made up 91.3% of the treated group and 81.8% of the control group, and the rest of the groups belonged to other ethnicities. However, because of the relatively small number of subjects under study, this circumstance might play a role in the results obtained.
In conclusion, we agree with the research findings of Anderson et al. (1) that women exposed to environmental tobacco smoke take up and metabolize the tobacco-specific carcinogen NNK, but if the aforementioned confounding factors were taken into account, the results of this extremely interesting research would be free of bias.
REFERENCES
1
Anderson KE, Carmella SG, Ye M, Bliss RL, Le C, Murphy L, Hecht SS. Metabolites of a tobacco-specific lung carcinogen in nonsmoking women exposed to environmental tobacco smoke. J Natl Cancer Inst 2001;93:378–81.
2 Wolf CR, Smith G. Cytochrome P450 CYP2D6. In: Vineis P, Malats N, Lang M, d'Errico A, Caposano N, Cuzick J, et al., eds. Metabolic polymorphism and susceptibility to cancer. Lyon (France): IARC Sci Publ 1999;148:209–29.
3 Hecht SS. Recent studies on mechanisms of bioactivation and detoxification of carcinogen 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific lung carcinogen. Crit Rev Toxicol 1996;26:163–81.[Web of Science][Medline]
4 Raunio H, Husgafvel-Pursianen K, Anttila S, Heitanen E, Hirvonen A, Pelkonen O. Diagnosis of polymorphism in carcinogen-activating and inactivating enzymes and cancer susceptibility—a review. Gene 1995;159:113–21.[CrossRef][Web of Science][Medline]
5 Wadelius M, Darj E, Frenne G, Rane A. Induction of CYP2D6 in pregnancy. Clin Pharmacol Ther 1997;62:400–7.[CrossRef][Web of Science][Medline]
6 Llerena A, Cobaleda L, Martinez C, Benitez J. Interethnic differences in drug metabolism: influence of genetic and environmental factors on debrisoquine hydroxylation phenotype. Eur J Drug Metab Pharmacokinet 1996;21:129–38.[Web of Science][Medline]
7
Morgan ET, Sewer MB, Iber H, Gonzalez FJ, Lee YH, Tukey RH et al. Physiological and pathophysiological regulation of cytochrome P450. Drug Metab Dispos 1998;26:1232–40.
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