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Re: Finnish hardwood

Dear Editor,

The absence of a significant nasal and ethmoid sinus cancer risk in Finland may be due to the low concentrations of polyphenols in domestic tree species as compared to imported wood from from more southern regions (1). The determination of the polyphenol content could be a good chemical surrogate for the detection of the species with carcinogenic properties (2).

1 Mämmelä P, Phenolics in selected European harwood species by liquid chromatography-electrospray ionisation mass spectromerty. Analyst, 2001; 126: 1535-1538.

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Re: Organic dust and lowered cancer rates: a dose-response relationship

Dear Editor,

The paper by Laakkonen et al., (1) reported a lower than expected rate of lung cancer in textile workers for men and women. The data in this study, as has been previously reported (2), suggest that a dose- response relationship exists for increasing cotton textile dust and lowered lung cancer rates. I would like to make several comments regarding this excellent report on dust exposure and respiratory cancer.

Numerous studies (3-7) have shown that exposure to organic dust, especially that having endotoxin, results in lower rates of lung cancer. These studies (2,3) have evaluated cotton textile and agricultural workers in regard to beneficial effects. Automobile workers exposed to contaminated machinery oils that contain high levels of endotoxin have also been reported to exhibit lower than expected rates of lung cancer (8). This concept has been termed the occupational hygiene hypothesis (9). When studies are adjusted for the major confounder of lung cancer, smoking, the benefits of exposure remained (3,6,7). Recently, a study (7) of women Chinese textile workers, whom few smoked, reported similar findings of reduced lung cancer. In this population, it was determined that the influence of the small number of smokers was negligible on cancer rates and that this population could be considered non-smokers (10). Historically, the reason given for lower rates in these occupational groups was a lower smoking rate, which was also suggested by Laakkonen. If the current studies of workers exposed to endotoxin-containing dust are analyzed in total, there appears to be a dose-response relationship (2), as indicated in Laakkonen’s study, and the confounder smoking is not responsible for these lower rates. A review of smoking rates indicates that cotton textile workers have a similar or higher rate than controls or the general population (11). Similar smoking rates in textile and control populations was initially shown by Henderson and Enterline (12), where rates of 51.9 and 51.2 percent for textile workers in 1967 and the US population (control) in 1970 were observed, respectively. It should also be noted that the epidemiological studies have been supported by animal investigations (13), which suggest a benefit against tumor metastasis. However, there have been epidemiological investigations that suggest exposure to cotton textile dust result in an increased risk of cancer (e.g. brain tumors) (14).

Recently, studies (10,15-17) of women Chinese textile workers have reported reduced rates of cancer in other organ systems beside the lung (e.g. liver, rectum, stomach and esophageal) . This indicates that the benefits of occupational exposure to endotoxin may not be limited to the respiratory system.

It has also been suggested that other occupational groups (e.g. sewage treatment workers) (18) that are exposed to endotoxin may be having reduced cancer rates from exposure. However, for the most part, few investigations on the beneficial effects of occupational exposure have been conducted. It should be noted, that one study (19) of smelter workers that were exposed to selenium also observed a lower than expected rate of lung cancer. This study along with those of agricultural and textile workers indicate that benefits from exposure may be more common than previously thought.

Based on the study by Laakkonen (1) and others (2), additional investigation on the benefits of occupational exposure is warranted. Few would have suggested years ago that exposure to dust in the occupational environment would have a benefit against cancer. However, evidence for such benefits existing is strong and the historical explanation of smoking being the responsible effect of lowered cancer rates in these occupational groups no longer appears applicable. Thus, benefits of organic dust exposure in reducing cancer should be considered a real effect and warrants intense investigation.

Some have suggested that exposure to endotoxin early in life, and possible in the occupational environment, also provides protection against allergy and/or asthma, which has been commonly called the hygiene hypothesis (20). It can be suggested that the mechanisms associated with the hygiene hypothesis and reduced cancer (occupational hygiene hypothesis) are the same or similar. Both appear to involve toll-like receptors and involvement of cytokines (6,11,20). For cancer, it has been suggested that this mechanisms involves pathways that results in apoptosis of the target cell, which is a cancer cell (6,11,21). There is likely an interrelationship between this anti-cancer activity and inflammation.

There are, however, risks of occupational disease (20) from exposure to endotoxin (22) and organic dust (23) and these risks are suggested to outweigh any benefits associated with reduced cancer rates.

References

1. Laakkonen A, Kyyronen P, Kauppinen T, Pukkala E. (2006). Occupational exposure to eight organic dusts and respiratory cancer. Occupational and Environmental Medicine.

2. Mastrangelo G, Fedeli U, Fadda E, Lange JH. 2002. Epidemiologic evidence of cancer risk in textile industry workers: a review and update. Toxicol Ind Health 18: 171-181.

3. Mastrangelo G, Marzia V, Milan G, Fadda E, Fedeli U, Lange JH (2004) An exposure-dependent reduction of lung cancer in dairy farmers. Indoor and Built Environment 13: 35-44.

4. Lange JH, Mastrangelo G, Fedeli U, Rylander R, Lee E. (2003). Endotoxin exposure and lung cancer mortality by type of farming: is there a hidden dose-response relationship? Annals of Agriculture and Environmental Medicine 10: 229-32.

5. Enterline, P.E., Sykora, J.L., Keleti, G,. Lange, J.H. 1985. Endotoxin, cotton dust and cancer. Lancet 2:934–35.

6. Mastrangelo G, Grange JM, Fadda E, Fedeli U, Buja A, Lange JH. (2005). Lung cancer risk: effect of dairy farming and the consequence of removing that occupational exposure. American Journal of Epidemiology. 161: 1037-1046.

7. Astrakianakis G, Seixas N, Camp J, Ray R, Gao DL, Wernli K, Thomas DB, Checkoway H. (2005) Reduced lung cancer risk associated with cotton dust exposure in women textile workers in Shanghai, China. American Journal of Epidemiology 161:S39 (abstract).

8. Schroeder JC, Tolbert PE, Eisen EA, Monson RR, Hallock MF, Smith TJ, Woskie SR, Hammond SK, Milton DK. (1997). Mortality studies of machinery fluid exposure in the automobile industry IV: a case-control study of lung cancer. Am J Ind Med 31: 525-33.

9. Lange JH, Rylander R, Fedeli U, Mastrangelo G. (2003). Extension of the hygiene hypothesis to the association of occupational endotoxin exposure with lower lung cancer risk. Journal of Allergy and Clinical Immunology 112: 219-20.

10. De Roos AJ, Ray RM, Gao DL, Wernli KJ, Fitzgibbons ED, Ziding F, Astrakianakis G, Thomas DB, Checkoway H. (2005). Colorectal cancer incidence among female textile workers in Shanghai, China: a case-control analysis of occupational exposures. Cancer Causes and Control 16:1177- 1188.

11. Lange JH (2006). Reduced lung cancer in workers exposed to organic dust: epidemiological and experimental evidence. Current Topics in Toxicology. (in press)

12. Henderson V, Enterline PE. (1973). An unusual mortality experience in cotton textile workers. Journal of Occupational Medicine.15:717-719.

13. Lange JH. (1992). Anticancer properties of inhaled cotton dust: a pilot experimental investigation. Journal of Environmental Science and Health (Part A). A27: 505-514.

14. Gold LS, De Roos AJ, Ray RM, Wernli K, Fitzgibbons ED, Gao DL, Astrakianakis G, Feng Z, Thomas D, Checkoway H. (2006). Brain tumors and occupational exposures in a cohort of female textile workers in Shanghai, China. Scand J Work Environ Health. 32:178-84.

15. Chang C-K, Astrakianakis G, Thomas DB, Seixas NS, Ray RM, Gao DL, Wernli KJ, Fitxgibbons ED, Vaughan TL, Checkoway H. Occupational exposures and risks of liver cancer among Shanghai female textile workers – a case- cohort study. International Journal of Epidemiology 2006;35: 361-9.

16. Fitzgibbins ED, Ray RM, Gao DL, LI W, Seixas NS, Camp JE, Astrakianakis G, Feng Z, Thomas DB, Checkoway H. (2006) Occupational risk factors for esophageal cancers among female textile workers in Shanghai, China. 163:717-25.

17. Wernli KJ, Fitzgibbins ED, Ray RM, Gao DL, LI W, Seixas NS, Camp JE, Astrakianakis G, Feng Z, Thomas DB, Checkoway H. (2006) Occupational risk factors for esophageal cancers among female textile workers in Shanghai, China. Am J Epidemiol 163:717-25. 18. Lange JH, Mastrangelo G and Thomulka KW (2003) Will sewage workers with endotoxin-related symptoms have benefit of reduced lung cancer? (Letter), Occupational and Environmental Medicine, 60:142-149.

19. Gerhardsson L, Brune D, Norberg IGF, Webster PO. (1985). Protective effect of selenium on lung cancer in smelter workers. Brit J Ind Med 42:617-26.

21. Lange JH, Mastrangelo G, Fadda E, Priolo G, Montemurro D, Grange JM,. (2005). Elevated lung cancer risk shortly after smoking cessation: is it due to reduction of endotoxin exposure? Medical Hypotheses. 65:534-541.

22. Thorn J, Rylander R. Inflammatory response after inhalation of bacterial endotoxin assessed by induced sputum techniques. Thorax 1998:53:1047-52.