Response: Re: Environmental Tobacco Smoke, Genetic Susceptibility, and Risk of Lung Cancer in Never-Smoking Women
Year: 2000
Type: article
Abstract: 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, α-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, gene–gene 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.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W1998999542