Affiliations of authors: W. P. Bennett, Division of Molecular Medicine, City of Hope Cancer Center and Beckman Research Institute, Duarte, CA; M. C. R. Alavanja (Division of Cancer Epidemiology and Genetics), C. C. Harris (Division of Basic Sciences), National Cancer Institute, Bethesda, MD.
Correspondence to: William P. Bennett, M.D., Division of Molecular Medicine, City of Hope Cancer Center and Beckman Research Institute, Fox Plaza S., Rm. 1001A, 1500 E. Duarte Rd., Duarte, CA 910103000 (e-mail: bbennett{at}coh. org).
Tricker's only valid criticism cites two negative studies (1,2) to refute our observation (3). Although the discrepancy is unexplained, early reports often conflict, and differences are usually reconciled by environmental, genetic, and lifestyle factors. For example, -tocopherol supplements may compensate for deficient GSTM1 activity (4), and dietary habits are known to modify risks of lung cancer. Therefore, culinary preferences might explain the discordant results, because our analyses (3) were adjusted for dietary intakes of fruits and vegetables, but those of Nyberg et al. (2) were not. [The abstract report by Malats et al. (1) cannot be assessed on this point.] Furthermore, genegene interactions between GSTM1 and CYP1A1 modulate risks in Japanese smokers [reviewed in (5)], and similar interactions among different genes are likely to occur in Caucasian nonsmokers.
Tricker attacks our point estimate of the interaction odds ratio (OR) for GSTM1 deletion and environmental tobacco smoke exposure by use of a misleading partial quotation from the editorial by Weinberg and Sandler (6). He misrepresents a paragraph in which they begin with the question, "How credible is this number?" (i.e., OR = 2.6), consider two sets of assumptions and analytic approaches, and conclude with "the confidence interval provided . . . for the interaction estimate of 2.6 does [emphasis in the original] include numbers as low as this [1.36], which is reassuring."
Tricker asserts that our findings require corroboration, and we fully agree that "additional studies are needed to confirm these observations," as stated in our report (3). Tricker summarizes his criticisms by declaring "it [is] hard to conclude whether individuals with germline polymorphisms in genes for enzymes that detoxify environmental genotoxins are at increased risk of lung cancer due to exposure to ETS [environmental tobacco smoke]." We agree that these studies are technically demanding. In fact, recognizing that "even small errors in the assessment of environmental or genetic factors can result in biased interaction parameters and substantially increased sample requirements" (7), corroboration of an effect linking GSTM1, environmental tobacco smoke, and risk of lung cancer will require substantially larger studies with detailed assessments of exposure and potentially confounding factors.
NOTES
W. P. Bennett and M. C. Alavanja contributed equally to the preparation of this correspondence.
REFERENCES
1 Malats N, Camus-Randon AM, Nyberg F, Ahrens W, Constantinescu V, Mukeria A, et al. Does GST M1 and T1 gene polymorphism modify environmental tobacco smoke effect on lung cancer? [abstract]. Proc Am Assoc Cancer Res 1998;39:182.
2 Nyberg F, Hou SM, Hemminki K, Lambert B, Pershagen G. Glutathione S-transferase mu1 and N-acetyltransferase 2 genetic polymorphisms and exposure to tobacco smoke in nonsmoking and smoking lung cancer patients and population controls. Cancer Epidemiol Biomarkers Prev 1998;7:87583.[Abstract]
3
Bennett WP, Alavanja MC, Blomeke B, Vahakangas KH, Castren K, Welsh JA, et al. Environmental tobacco smoke, genetic susceptibility, and risk of lung cancer in never-smoking women. J Natl Cancer Inst 1999;91:200914.
4
Woodson K, Stewart C, Barrett M, Bhat NK, Virtamo J, Taylor PR, et al. Effect of vitamin intervention on the relationship between GSTM1, smoking, and lung cancer risk among male smokers. Cancer Epidemiol Biomarkers Prev 1999;8:96570.
5
Bartsch H, Nair U, Risch A, Rojas M, Wikman H, Alexandrov K. Genetic polymorphism of CYP genes, alone or in combination, as a risk modifier of tobacco-related cancers. Cancer Epidemiol Biomarkers Prev 2000;9:328.
6
Weinberg CR, Sandler DP. Gene-by-environment interaction for passive smoking and glutathione S-transferase M1? [editorial]. J Natl Cancer Inst 1999;91:19856.
7
Garcia-Closas M, Rothman N, Lubin J. Misclassification in casecontrol studies of geneenvironment interactions: assessment of bias and sample size. Cancer Epidemiol Biomarkers Prev 1999;8:104350.
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