Causal and nonlinear models of cancer risk among autoworkers.
Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, R01-OH-008927, 2011 Aug; :1-10
Metalworking fluids (MWF) are complex mixtures of oils and chemicals widely used in industry to cool and lubricate metal operations. There are millions of US workers exposed to MWF and their use is increasing internationally despite the presence of known carcinogens, such as polycyclic aromatic hydrocarbons in oil-based fluids, and ethanolamines and nitrosamines in water-based fluids. Our cohort of 46,397 United Autoworkers at General Motors (UAW-GM) is the only existing study with quantitative estimates of lifetime exposure to both water- and oil-based MWF. We have taken advantage of this resource by extending vital status follow-up from 50 to 60 years and linking with the Michigan Cancer Registry to identify incident cancers diagnosed in the cohort over the past 20 years. Based on the cancer incidence data, we have found new positive associations between straight MWF exposure and bladder cancer and malignant melanoma. For both cancers, the hazard rate ratio rose to 2-fold in the highest quintile of cumulative exposure to straight MWF. We also reported standardized incidence ratios (SIRs) for all cancers in the sub-cohort of female autoworkers. We found an elevated SIR of 2.71 (95% CI: 1.94, 3.69) for cervical cancer incidence, though there was no evidence of any association with MWF exposure. In a new effort to tease out the common components of oil-and water-based MWF, we developed a set of new exposure metrics and evaluated them with respect to cancer incidence. Laryngeal and bladder cancer were most strongly associated with PAH. Rectal cancer was associated with synthetics as well as straight MWF. Protective effects were observed for biocide exposure and lung and stomach cancer; biocide may be a surrogate for endotoxin contamination of the water-based soluble and synthetic fluids. Perhaps the paper with the greatest potential impact is the one where we apply g-estimation to reduce healthy worker survivor bias. G-estimation is one of several new causal methods in epidemiology. It was originally developed to address HWE, but until our recent work it had never been applied in an occupational cohort study. Results of our analysis suggest that exposure to straight MWF increases risk of mortality from all causes of death combined, COPD, ischemic heart disease and all cancers combined, as well as lung cancer and prostate cancer in particular. This is the first study to report a positive association between oil-based MWF, COPD ischemic heart disease and lung cancer mortality. By providing a roadmap for the application of g-estimation, we hope to encourage more widespread use of these innovative and critically important new epidemiologic methods for identifying occupational causes of disease.
Automotive-industry; Metallic-compounds; Metal-compounds; Oils; Chemical-composition; Chemical-properties; Lubricating-oils; Lubricants; Carcinogens; Polycyclic-aromatic-hydrocarbons; Nitrosamines; Exposure-levels; Risk-factors; Bladder-cancer; Cancer; Hazards; Humans; Men; Women; Epidemiology; Cutting-oils
Ellen A. Eisen, ScD, School of Public Health, University of California Berkeley, Berkeley, CA 94720-7360
Final Grant Report
NTIS Accession No.
National Institute for Occupational Safety and Health
University of California, Berkeley