© The Author 2007. Published by Oxford University Press.
EDITORIALS |
Endotoxins in Lung Cancer Prevention
Correspondence to: Paolo Boffetta, MD, Gene–Environment Epidemiology Group, International Agency for Research on Cancer, 150 cours Albert Thomas, 69008 Lyon, France (e-mail: boffetta{at}iarc.fr).
In this issue of the Journal, Astrakianakis et al. (1) report an inverse association between exposure to endotoxins of women in the textile industry in Shanghai and risk of lung cancer. This study has the usual potential limitations of epidemiologic research, and the protective effect against lung cancer observed among female Chinese textile workers with high endotoxin exposure may be one of the many associations reported in cancer epidemiology that are not confirmed by subsequent studies. However, this finding is potentially important for lung cancer research for several reasons.
A decreased risk of lung cancer has been consistently reported among different populations potentially exposed to endotoxins, in particular, textile workers (2). A lower level of tobacco smoking among textile workers has been often invoked to explain this result, but the empirical evidence supporting such a hypothesis is not strong (3). Furthermore, only large differences between the smoking habits of textile workers and those of the rest of the population would explain the reduction in lung cancer mortality observed in many studies.
An alternative explanation is that the reduced risk of lung cancer (or at least part of it) is real and is due to agents present in the environment of textile workers. The study by Astrakianakis et al. provides evidence in favor of a cancer-preventive effect of endotoxins in humans. The quality of the study lies on the detailed assessment of exposure to endotoxins: this study indeed demonstrates the importance of exposure assessment, by use of either biologic markers or traditional approaches, to enhance the ability of cancer epidemiology to detect etiologically relevant associations.
Although very solid, the study of Chinese textile workers is not exempt from limitations. This cohort of female workers was composed of a low proportion of smokers, and only 11% of the cases of lung cancer occurred among ever smokers. Although a similar protective effect from high endotoxin exposure was observed among both ever smokers and never smokers, the precision of the risk estimate in the former group was modest. Because, in the United States and in most other populations, most cases of lung cancer occur among ever smokers (4), a precise estimate of the effect of endotoxin exposure among ever smokers is essential when the potential impact of endotoxins is assessed on a broader scale.
Although the focus of the study by Astrakianakis et al. on endotoxins was justified by previous experimental results, workers could also be exposed to other unmeasured agents, which could be responsible for the observed effect. In addition, endotoxins are a heterogeneous group of compounds, but the study did not investigate individual endotoxins. For clinical application, one would like to know which endotoxin (if any) exerts a chemopreventive effect. This information is crucial if an endotoxin-based lung cancer prevention trial is to be designed.
The weakest part of the study, however, lies in the limited understanding of the potential mechanisms of the cancer-preventive action of endotoxins. Although occasionally results of epidemiologic studies showing an association between environmental exposures and cancer risk have preceded elucidation of the underlying mechanisms of action, understanding of the process of lung carcinogenesis in humans has greatly increased in the last years, and the requirement that results from epidemiology and biology be consistent and mutually supportive has become more important.
Results of the study by Astrakianakis et al. are strongly suggestive that endotoxin exposure is associated with a reduced risk of lung cancer, but potential confounding and lack of strong supportive mechanistic evidence prevent stronger conclusions. These considerations, coupled with imperfect knowledge on potential health risks of endotoxins, argue against the implementation of an endotoxin-based intervention against lung cancer in the near future. Extrapolation of these results to populations of smokers at high risk of lung cancer is particularly problematic, as shown by results of the lung cancer prevention trials based on 
-carotene administration (5). Great caution should be exercised by all when moving from the results of observational studies of the effects of complex mixtures to interventions aimed at cancer prevention.
REFERENCES
(1) Astrakianakis G, Seixas NS, Ray R, Camp JE, Gao DL, Feng Z, et al. (2007) Lung cancer risk among female textile workers exposed to endotoxin. J Natl Cancer Inst 99:357–64.
(2) Mastrangelo G, Fedeli U, Fadda E, Milan G, Lange JH. (2002) Epidemiologic evidence of cancer risk in textile industry workers: a review and update. Toxicol Ind Health 18:171–81.
(3) Lee DJ, LeBlanc W, Fleming LE, Gomez-Marin O, Pitman T. (2004) Trends in US smoking rates in occupational groups: the National Health Interview Survey 1987-1994. J Occup Environ Med 46:538–48.[CrossRef][Web of Science][Medline]
(4) International Agency for Research on Cancer. (2004) Tobacco smoke. Tobacco smoke and involuntary smoking. IARC monographs on the evaluation of carcinogenic risks to humans. (IARC, Lyon (France)) Vol. 83:51–1187.
(5) International Agency for Research on Cancer. (1998) Carotenoids. IARC handbooks of cancer prevention. (IARC, Lyon (France)) Vol. 2:.
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J Natl Cancer Inst 2007 99: 337.
J Natl Cancer Inst 2007 99: 337.
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