CORRESPONDENCE

RESPONSE: Re: Metabolites of a Tobacco-Specific Lung Carcinogen in Nonsmoking Women Exposed to Environmental Tobacco Smoke

Kristin E. Anderson , Stephen S. Hecht, Robin L. Bliss, Chap Le

Affiliations of authors: K. E. Anderson (Division of Epidemiology, School of Public Health), S. S. Hecht, R. L. Bliss, C. Le, Comprehensive Cancer Center, University of Minnesota, Minneapolis.

Correspondence to: Kristin E. Anderson, Ph.D., Division of Epidemiology, University of Minnesota, 1300 S. Second St., #300, Minneapolis, MN 55454 (e-mail: anderson_k{at}epi.umn.edu).

My colleagues and I thank Drs. Chobanyan and Nersesyan for their thoughtful letter and comments regarding our recent report (1). They expressed concern over several potential confounders in our study, namely, age, sex, alcohol consumption, and race, because these may modify cytochrome P450 activity.

Clearly, any hypothesized differences in NNK metabolism due to these factors would have to be tested directly; however, on the basis of our study data, we will address the concerns they raised. (We did not assess alcohol consumption in this study and, therefore, cannot address this issue.)

Drs. Chobanyan and Nersesyan cited the cytochromes P450 CYP2D6 and/or CYP2E1 as activators of NNK. Although there is evidence for the involvement of CYP2D6 and CYP2E1 in the metabolism of NNK, these are not the most important catalysts. The cytochromes P450 CYP2A13, CYP2A6, CYP3A4, and CYP1A2 have far greater activity (2,3). This aside, we can still consider the issue of potential confounding by the factors listed above.

They noted the difference in mean ages between the exposed and unexposed women. We must point out that the difference in mean ages between the two groups was not statistically significant. Nonetheless, during our analysis, we used analysis of covariance and found that adjustment for age did not substantively alter any of the findings, and the differences detected between the exposed and unexposed women remained statistically significant.

Given that age was not a factor, we have no evidence to suggest that menopausal status is a factor in our findings. Furthermore, if the exposed women in our study were compared with the unexposed males (instead of the unexposed females), our results were virtually unchanged and all differences remained statistically significant.

It is indeed plausible that there are racial differences with respect to NNK metabolism. However, our study results were not substantively altered when our analyses were restricted to Caucasians; all differences remained statistically significant.

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.[Abstract/Free Full Text]

2 Su T, Bao Z, Zhang QY, Smith TJ, Hong JY, Ding X. Human cytochrome P450 CYP2A13: predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Cancer Res 2000;60:5074–9.[Abstract/Free Full Text]

3 Hecht SS. Biochemistry, biology, and carcinogenicity of tobacco-specific N-nitrosamines. Chem Res Toxicol 1998;11:559–603.[Medline]



             
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