LETTER TO THE EDITOR

Endotoxin: does it have a role in prevention of lung cancer

J H Lange

Envirosafe Training and Consultants Inc, P O Box 114022, Pittsburgh, PA 15239, USA

Keywords: endotoxin; lung cancer

The paper by Drs Douwes, Pearce and Heederik provides an interesting overview of how endotoxin may interact in atopy and asthma. It discusses issues as to whether endotoxin plays a role in prevention of atopy and asthma or may, in fact, be a contributor to these respiratory diseases. However, readers should be aware that there is another important issue, although controversial, related to endotoxin and the lung—that is, does endotoxin exposure in some occupational groups result in reduced lung cancer rates?

There have been a number of reports^2–8 suggesting that endotoxin exposure, mostly in organic dusts, results in reduced lung cancer rates. This reduced lung cancer rate was first identified in textile workers^2,3 and later in agricultural^4,5 and other groups^6,7 exposed to endotoxin. Experimental studies^9,10 have supported epidemiological findings and clinical trials^11,12 have been undertaken to evaluate this agent and the effectiveness of its immunomediators in cancer treatments. Although the concept of a beneficial effect from occupational exposure is novel,⁵ it has been reported in at least one other occupational epidemiological investigation of reduced lung cancer rates for a potentially better recognised anticancer agent (selenium).^13,14 Most investigators disagree with any benefit from occupational exposure and attribute these findings to various forms of selection bias (healthy worker effect) and lower rates of smokers in study populations (compared with controls).^4,5,7

Certainly exposure to organic dusts and endotoxin does not occur without risk. There are numerous reports of the detrimental outcomes associated with such exposures.⁸ However, when various forms of bias are evaluated, there appears to be in some studies an inability to explain the reduced lung cancer rates.^2,4,7

It is encouraged that scientists accept the concept that there is an alternative view for lower lung cancer rates in some study populations. Even though this challenges prevailing thought and conventional thinking, we must remember that tradition dies hard and the birth of a new idea requires a creative and innovative spirit.¹⁵

1. Douwes J, Pearce N, Heederik D. Does environmental endotoxin exposure prevent asthma? Thorax 2002;57:86–90.[Abstract/Free Full Text]
2. Enterline PE, Sykora JL, Keleti G, et al. Endotoxin, cotton dust and cancer. Lancet 1985;ii:934–5.
3. Rylander R. Environmental exposures with decreased risks for lung cancer. Int J Epidemiol 1990;19:567–72.
4. Mastrangelo G, Marzia V, Marcer G. Reduced lung cancer mortality in dairy farmers: is endotoxin exposure the key factor?. Am J Ind Med 1996;30:601–9.[CrossRef][Medline]
5. Lange JH. Reduced cancer rates in agricultural workers: a benefit of environmental and occupational endotoxin exposure. Med Hypotheses 2000;55:383–5.[CrossRef][Medline]
6. Schroeder JC, Tolbert PE, Eisen EA, et al. Mortality studies of machining fluid exposure in the automobile industry. IV: A case-control study of lung cancer. Am J Ind Med 1997;31:525–33.[CrossRef][Medline]
7. Rapiti E, Sperati A, Fano V, et al. Mortality among workers at municipal waste incinerators in Rome: a retrospective cohort study. Am J Ind Med 1997;31:659–61.[CrossRef][Medline]
8. Hodgson JT, Jones RD. Mortality of workers in the British cotton industry in 1968–1984. Scand J Work Environ Health 1990;16:113–20.[Medline]
9. Lange JH. Anti-cancer properties if inhaled cotton dust: a pilot experimental investigation. J Environ Sci Health 1992;27A:505–14.
10. Lange JH. An experimental study of anti-cancer properties of aerosolized endotoxin: application to human epidemiological studies. J Occup Med Toxicol 1992;1:377–82.
11. Engelhardt R, Mackensen A, Galanos C. Phase 1 trial of intravenously administered endotoxin (Salmonella abortus equi) in cancer patients. Cancer Res 1991;51:2524–30.[Abstract/Free Full Text]
12. Otto F, Schmid P, Mackensen A, et al. Phase II trial if intravenous endotoxin in patients with colorectal and non-small cell lung cancer. Eur J Cancer 1996;32A:1712–8.
13. Gerhardsson L, Brune D, Norberg IFG, et al. Protective effect of selenium on lung cancer in smelter workers. Br J Ind Med 1985;42:617–26.[Medline]
14. Lange JH, Talbott EO, Baffone KM, et al. Anti-cancer activities of selenium. Med Hypotheses 1987;23:443–7.[Medline]
15. Paydarfar D, Schwartz WJ. Editorial: an algorithm for discovery. Science 2001;292:13.[Medline]

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