Dear Editor

Endotoxin: it’s activity in atopy and asthma is not the only controversial issue – does it play a role in prevention of lung cancer in some occupational populations

The paper Does environmental endotoxin exposure prevent asthma? by Douwes et al. provides an interesting overview of how endotoxin may interact in atopy and asthma. This paper 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 [1-7] 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[1,2] and later in agricultural[3,4] and other groups[5,6] exposed to endotoxin. Experimental studies[8,9] have supported epidemiological findings and clinical trials[10,11] have been undertaken to evaluate this agent and it’s immuno-mediators effectiveness in cancer treatments. Although the concept of a beneficial effect from occupational exposure is novel,[4] it has been reported in at least one other occupational epidemiological investigation of reduced lung cancer rates for a potentially better-recognized anticancer agent (selenium) .[12,13] Most investigators disagree with any benefit from occupational exposure and attribute these findings to various forms of selection bias (e.g. healthy worker effect) and lower rates of smokers in study populations (as compared to controls).[3,4,6]

Certainly exposure to organic dusts and endotoxin does not occur with out risk. There are numerous reports of the detrimental outcomes associated with such exposures.[13] However, when various forms of bias are evaluated, there appears to be in some studies an inability to explain the reduced lung cancer rates.[1,3,6]

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 sprit.[14]

References

(1) Enterline PE, Sykora JL, Keleti G, and Lange JH. Endotoxin, cotton dust and cancer. Lancet 1985;2:934-935.

(2) Rylander R. Environmental exposures with decreased risks for lung cancer. Int J Epidemiol 1990;19: 567-572

(3) Mastrangelo G, Marzia V, and Marcer G. Reduced lung cancer mortality in diary farmers: is endotoxin exposure the key factor? Am J Ind Med 1996;30:601-609.

(4) Lange JH. Reduced cancer rates in agricultural workers: a benefit of environmental and occupational endotoxin exposure. Med Hypotheses 2000;55: 383-385

(5) Schroeder JC, Tolbert PE, Eisen EA, Monson RR, Hallock MF, Smith TJ, Woskie SR, Hammond SK, and Milton DK. Mortality studies of machining fluid exposure in the automile industry IV: a case-control study of lung cancer. Am J Ind Med 1997; 31: 525-533.

(6) Rapiti E, Sperati A, Fano V, Dell’Orco V, Forastiere F. Mortality among workers at municipal waste incinerators in Rome: a retrospective cohort study. Am J Ind Med 1997; 31: 659-661

(7) Hodgson JT and Jones RD. Mortality of workers in the British cotton industry in 1968-1984. Scan J Work Environ Health 1990;16:113- 120.

(8) Lange, JH (1992) Anti-cancer properties if inhaled cotton dust: a pilot experimental investigation. J Environ Sci and Health 1992;27A: 505-514.

(9) Lange JH. An experimental study of anti-cancer properties of aerosolized endotoxin: application to human epidemiological studies. J Occup Med And Toxicology1:377-382.

(10) Engelhardt R, Mackensen A and Galanos C. Phase 1 trial of intravenously administered endotoxin (Salmonella abortus equi) in cancer patients. Cancer Research 1991;51:2524-2530.

(11) Otto F, Schmid P, Mackensen A, Wehr U, Siez A, Braun M, Galanos C, Mertelsmann R, and Engelhardt R. Phase II trail if intravenous endotoxin in patients with colorectal and non-small cell lung cancer. European J Cancer 1996;32A:1712-1718.

(12) Gerhardsson L, Brune D, Norberg IFG, and Webster PO. Protective effect of selenium on lung cancer in smelter workers. Br J Ind Med 1985;42:617-626.

(13) Lange JH, Talbott EO, Baffone KM, Weyel DA, Soboslay EG, Koros AMC, and Sykora JL. Anti-cancer activities of selenium. Med Hypotheses 1987;23:443-447.

(14) Paydarfar D and Schwartz WJ. Editorial, An algorithm for discovery. Science 2001;292: 13.