American Journal of Epidemiology Advance Access originally published online on April 18, 2007
American Journal of Epidemiology 2007 165(12):1462-1463; doi:10.1093/aje/kwm103
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LETTERS TO THE EDITOR |
AN AUTHOR REPLIES
University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232
(e-mail: taiolien{at}upmc.edu)
We thank Dr. Weiss for his letter (1). We strongly agree with him regarding the need to defend epidemiologic studies with high-quality data. We wish to point out, however, that Dr. Weiss has not correctly interpreted our data. There is no suggestion in our paper (2) that, as Dr. Weiss puts it, "asbestos exposure [is] associated with a reduction in risk of lung cancer" (1, p. 1462). The paper instead reports that "a significant negative interaction was observed between being occupationally exposed and GSTT1: exposed subjects for whom GSTT1 was present were at higher risk of lung cancer than exposed subjects carrying the GSTT1 null genotype" (2, p. 1036). This is equivalent to the many studies showing that certain genetic variants reduce the risk of lung cancer for smokers as compared with persons with other genotypes; it certainly does not mean that people with these variants should be encouraged to smoke. On behalf of the 42 authors who contributed the data permitting our study, I hope this addresses the misunderstanding that Dr. Weiss, and perhaps others who are less familiar with the field of genetic susceptibility to environmental carcinogenesis, apparently came away with from the paper.
As regards exposure information, we of course agree that such information is vital for drawing definitive conclusions. However, we remind Dr. Weiss and other readers that our paper presents results from a pooled analysis, in which many investigators contributed original data from their own studies. While genotyping methodology has become standard and routine, unfortunately exposure assessment may be quite variable across laboratories, which is why we do not draw any definitive conclusions regarding exposure (defined very loosely as occupational exposure and asbestos exposure). As we indicated in the paper (2), only a small fraction (35 percent) of the subjects had information on occupational exposure, thus making interpretation of the results very limited.
The main point in our article is that contrary to earlier expectations, the glutathione S-transferase theta 1 (GSTT1) null allele is not always a risk factor for lung cancer and other cancers, as it was assumed to be in the past, but has turned out to be protective against some environmental carcinogenic exposures. Similar results have in fact been obtained by a number of laboratories in individual studies including intermediate markers of DNA damage (3–9). As we comment in the Discussion (2), this may be due to the fact that some compounds present in occupational settings are known substrates of GSTT1. Dichloromethane and other halogenated compounds may be metabolized by GSTT1 into mutagenic intermediates; thus, GSTT1-positive subjects might be more prone than GSTT1-null subjects to the genotoxic action of halogenated compounds via the GSTT1 pathway (10).
We thank Dr. Weiss for his interest in our paper and wish to assure him that the "descendants" of Feinstein (11) would be hard-pressed to find any comfort in our article if they understood its content.
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ACKNOWLEDGMENTS |
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Conflict of interest: none declared.
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References |
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 TOP References |
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- Weiss NS. Re: "Meta- and pooled analysis of GSTT1 and lung cancer: a HuGE-GSEC review." (Letter). Am J Epidemiol (2007) 165:1462.
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[Abstract/Free Full Text] - Brockstedt U, Krajinovic M, Richer C, et al. Analyses of bulky DNA adduct levels in human breast tissue and genetic polymorphisms of cytochromes P450 (CYPs), myeloperoxidase (MPO), quinone oxidoreductase (NQO1), and glutathione S transferases (GSTs). Mutat Res (2002) 516:41–7.[Web of Science][Medline]
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[Abstract/Free Full Text] - Marcon F, Andreoli C, Rossi S, et al. Assessment of individual sensitivity to ionizing radiation and DNA repair efficiency in a healthy population. Mutat Res (2003) 541:1–8.[Web of Science][Medline]
- Scarpato R, Migliore L, Hirvonen A, et al. Cytogenetic monitoring of occupational exposure to pesticides: characterization of GSTM1, GSTT1, and NAT2 genotypes. Environ Mol Mutagen (1996) 27:263–9.[CrossRef][Web of Science][Medline]
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[Abstract/Free Full Text] - Landi S. Mammalian class theta GST and differential susceptibility to carcinogens: a review. Mutat Res (2000) 463:247–83.[CrossRef][Web of Science][Medline]
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  RE: "META- AND POOLED ANALYSIS OF GSTT1 AND LUNG CANCER: A HUGE-GSEC REVIEW" Am. J. Epidemiol., August 1, 2007; 166(3): 366 - 366. [Full Text] [PDF]
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