School of Public Health and Community Medicine - University of Washington - Autumn 2006

In one of the largest occupational epidemiology cohort studies ever conducted, a research team led by Professor Harvey Checkoway found that a certain type of bacterial toxin might protect textile workers from lung and other cancers.

Shanghai worker cleans a spinning machine.
Photo by Harvey Checkoway

The team, including Checkoway, Professor Noah Seixas, Senior Lecturer Janice Camp, former graduate student George Astrakianakis, and colleagues from the Fred Hutchinson Cancer Research Center and the Shanghai Textile Industry Bureau, investigated associations between workplace exposures and cancer risks among 267,400 women textile workers in Shanghai, China. Checkoway received a grant from the National Cancer Institute to conduct the study.

The study was conducted in two phases. The first compared cancer rates in the textile worker cohort with prevailing rates in Shanghai women from 1989 through 1998. The second, more in-depth, analysis compared workplace exposure to dusts, chemicals, and physical agents experienced by women who developed cancer with those of other women textile workers who did not develop cancer. A detailed job-exposure matrix was developed specifically for the Shanghai textile industry to enable dose-response analyses.

Overall, the cohort’s cancer incidence did not seem unusually high when comparisons were made with Shanghai city rates. In fact, reduced risks were observed for a number of cancers, including lung, esophagus, stomach, rectum, cervix, ovary, and urinary bladder. The lower-than-expected risks for lung and bladder cancers may be attributed to a lower proportion of current or former smokers in the cohort (3%) compared with the general population of Shanghai women (7%).

More interestingly, the lung cancer result may have been strongly influenced by cotton dust and endotoxin exposures, which may have a protective effect on lung and several other cancers. Endotoxins are a particular type of toxin bound to gram negative bacterial cells that are released when the cells are disrupted. These bacteria, which turn pink in a laboratory technique called a gram stain, contain an outer membrane outside the cell wall. Cotton processing is the predominant source of endotoxin in this industry.

Based on prior studies, the researchers had expected to find an inverse dose-response curve for cumulative exposure to endotoxin and lung cancer, but they were surprised by the strength of the association in this study. The apparently protective effect of endotoxin was most prominent for exposures that occurred early in women’s working careers. Even more surprising were unanticipated results showing similar patterns of reduced risks associated with endotoxin for cancers of the esophagus, stomach, pancreas, liver, breast, and ovary.

Checkoway’s team built its research on the findings of previous epidemiologic research that linked cotton dust with lung cancer, formaldehyde with cancers of the nasal passages (nasopharyngeal cancer), colon cancer with synthetic fibers, breast cancer with exposures to electromagnetic fields (EMF) and solvents, and lung cancer with silica exposure.

The UW team did not observe any strong or consistent associations for nasopharyngeal, colon, rectal, bladder, brain, or thyroid cancers. Silica, although not a widespread exposure in the textile industry, was related to an increased lung cancer risk. Silica has been established as a lung carcinogen from research in many other industrial settings. Checkoway has a separate NIOSH-funded grant to examine breast cancer risk in the same cohort in relation to working on night or rotating shifts. Camp and Professor Michael Yost are co-investigators.

Checkoway believes that this investigation was the largest, most comprehensive epidemiologic study of textile industry exposures and cancer ever conducted. In addition to the large size of the cohort, other notable strengths of the study were the use of data about cancer incidence, rather than mortality, and the reconstruction of historical exposures to specific agents that enabled dose-response analyses.

Shanghai provides an excellent setting for occupational epidemiologic research, he said, because the Shanghai Anti-epidemic Bureau (currently, the Shanghai Municipal Center for Disease Control) has conducted detailed factory inspections since the 1950s, identifying exposures to textile dusts (cotton, wool, synthetic fibers, silk), solvents, bleaching agents, acids, bases, caustics, formaldehyde, dyes, inks, resins, coatings, metals, lubricants, silica, pesticides, and electromagnetic fields.

Epidemiology Professor David Thomas had previously studied this cohort of workers for a randomized intervention trial of the efficacy of breast-self exam. The trial defined the cohort and provided the collaborative research infrastructure in Shanghai for this occupational cancer study.

There is precedent in the literature for an apparently protective effect of endotoxin against lung cancer. In the 1970s, findings from occupational cohort studies demonstrated reduced risks for lung cancer among cotton textile workers in the United States and Great Britain.

These results were regarded as somewhat surprising when first observed, but the previous studies lacked the type of quantitative exposure assessment available in Shanghai. The underlying biological explanation for a protective effect of endotoxin against cancer might result from complex interactions between the innate and acquired immune systems. More experimental research is needed to clarify mechanisms.

For further reading

Astrakianakis G, Seixas NS, Camp JE, Christiani DC, Feng Z, Thomas DB, Checkoway H. Modeling, estimation and validation of cotton dust and endotoxin exposures in Chinese textile operations. Ann Occup Hyg 2006 Aug;50(6):573–582.

Astrakianakis G, Seixas NS, Ray R, Camp JE, Gao DL, Feng Z, Wernli K, Fitzgibbons ED, Thomas DB, Checkoway H. Reduced risk of lung cancer among female textile workers exposed to endotoxin. J Natl Cancer Inst, submitted.