Multistage Modeling of Lung Cancer Mortality Among Arsenic-Exposed Copper-Smelter Workers (original) (raw)
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Environmental health …, 2008
Background Inhalation of high levels of airborne inorganic arsenic is a recognized cause of respiratory cancer. Although multiple epidemiologic studies have demonstrated this association, there have been few analyses of the mathematical relationship between cumulative arsenic exposure and risk of respiratory cancer, and no assessment as to whether and how arsenic concentration may modify this association.Objectives The objective is an evaluation of the shape of the relationship between respiratory cancer mortality and cumulative inhaled arsenic exposure among copper smelter workers, and the modification of that relationship by arsenic concentration.Methods We used Poisson regression methods to analyze data from a cohort of arsenic-exposed copper smelter workers under a linear-exponential model for the excess relative risk.Results Within categories of arsenic concentration, the association between respiratory cancer and cumulative arsenic exposure was consistent with linearity. The slope of the linear relationship with cumulative exposure increased with increasing arsenic concentration category.Conclusions Our results suggested a direct concentration effect from inhaled inorganic arsenic, whereby the excess relative risk for a fixed cumulative exposure was greater when delivered at a higher concentration and shorter duration than when delivered at a lower concentration and longer duration.
American Journal of Industrial Medicine, 2009
Objective To evaluate the long-term mortality experience of workers exposed to arsenic, cadmium, and other substances at a copper mine and smelter in Copperhill, Tennessee studied earlier as part of an industry-wide study. Methods Subjects were 2,422 male workers employed three or more years in the smelter or mill between 1/1/46 until the plant strike and scale-down of operations in April 1996. Vital status was determined through 2000 for 99.4% of subjects and cause of death for 91.3% of 878 deaths. Historical exposures were estimated for lead, SO 2 , arsenic, cadmium, dust, and cobalt. We computed standardized mortality ratios (SMRs) based on U.S. and local county rates and modeled internal relative risks (RRs). Results We observed overall deficits in deaths based on national and local county comparisons from all causes, all cancers and most of the cause of death categories examined. We found limited evidence of increasing mortality risks from cerebrovascular disease with increasing duration and cumulative arsenic exposure, but no evidence of an exposure-response relationship for cadmium exposure and bronchitis. Conclusions Our limited evidence of an association between inhaled arsenic exposure and CVD is an exploratory finding not observed in other epidemiology studies of more highly exposed occupational populations. Possible alternative explanations include chance alone and uncontrolled confounding or effect modification by co-exposures or other factors correlated with arsenic exposure and unique to the Copperhill facility.
Arsenic, Tobacco Smoke, and Occupation
Epidemiology, 2013
Background: Millions of people worldwide are exposed to arsenic in drinking water, and many are likely coexposed to other agents that could substantially increase their risks of arsenic-related cancer. Methods: We performed a case-control study of multiple chemical exposures in 538 lung and bladder cancer cases and 640 controls in northern chile, an area with formerly high drinking water arsenic concentrations. Detailed information was collected on lifetime arsenic exposure, smoking, secondhand smoke, and other known or suspected carcinogens, including asbestos, silica, and wood dust. Results: Very high lung and bladder cancer odds ratios (Ors), and evidence of greater than additive effects, were seen in people exposed to arsenic concentrations >335 µg/l and who were tobacco smokers (Or = 16, 95% confidence interval = 6.5-40 for lung cancer; and Or = 23 [8.2-66] for bladder cancer; rothman Synergy indices = 4.0 [1.7-9.4] and 2.0 [0.92-4.5], respectively). evidence of greater than additive effects were also seen in people coexposed to arsenic and secondhand tobacco smoke and several other known or suspected carcinogens, including asbestos, silica, and wood dust. Conclusions: these findings suggest that people coexposed to arsenic and other known or suspected carcinogens have very high risks of lung or bladder cancer.
Occupational and Environmental Medicine, 1996
Objective-This investigation sought to examine whether methods proposed to control the healthy worker survivor effect would influence the shape or magnitude of the dose-response curve for respiratory cancer induced by arsenic. Methods-Results from an unadjusted analysis are compared with results obtained by applying four different methods for control of the healthy worker survivor effect to data on arsenic exposure and respiratory cancer. The four methods are: exposure lag, adjustment for work status, cohort restriction, and the G null test. Results-Cohort restriction gave erratic results depending upon the minimum years of follow up used. Exposure lag substantially increased the rate ratios and a non-linear shape (decreasing slope) compared with an unlagged analysis. Adjusting
Lung Cancer in a US Population with Low to Moderate Arsenic Exposure
Environmental Health Perspectives, 2009
Little is known about the carcinogenic potential of arsenic in areas with low to moderate concentrations of arsenic (< 100 µg/L) in drinking water. oBjectives: We examined associations between arsenic and lung cancer. Methods: A population-based case-control study of primary incident lung cancer was conducted in 10 counties in two U.S. states, New Hampshire and Vermont. The study included 223 lung cancer cases and 238 controls, each of whom provided toenail clippings for arsenic exposure measurement by inductively coupled-plasma mass spectrometry. We estimated odds ratios (ORs) of the association between arsenic exposure and lung cancer using unconditional logistic regression with adjustment for potential confounders (age, sex, race/ethnicity, smoking pack-years, education, body mass index, fish servings per week, and toenail selenium level). results: Arsenic exposure was associated with small-cell and squamous-cell carcinoma of the lung [OR = 2.75; 95% confidence interval (CI), 1.00-7.57] for toenail arsenic concentration ≥ 0.114 µg/g, versus < 0.05 µg/g. A history of lung disease (bronchitis, chronic obstructive pulmonary disease, or fibrosis) was positively associated with lung cancer (OR = 2.86; 95% CI, 1.39-5.91). We also observed an elevated risk of lung cancer among participants with a history of lung disease and toenail arsenic ≥ 0.05 µg/g (OR = 4.78; 95% CI, 1.87-12.2) than among individuals with low toenail arsenic and no history of lung disease. conclusion: Although this study supports the possibility of an increased risk of specific lung cancer histologic types at lower levels of arsenic exposure, we recommend large-scale populationbased studies. key words: arsenic, bronchitis, chronic obstructive pulmonary disease, lung cancer, lung diseases, New Hampshire, pulmonary fibrosis, small-cell carcinoma, smoking, Vermont. Environ Health
Journal of environmental and public health, 2016
Background. To examine whether the US EPA (2010) lung cancer risk estimate derived from the high arsenic exposures (10-934 µg/L) in southwest Taiwan accurately predicts the US experience from low arsenic exposures (3-59 µg/L). Methods. Analyses have been limited to US counties solely dependent on underground sources for their drinking water supply with median arsenic levels of ≥3 µg/L. Results. Cancer risks (slopes) were found to be indistinguishable from zero for males and females. The addition of arsenic level did not significantly increase the explanatory power of the models. Stratified, or categorical, analysis yielded relative risks that hover about 1.00. The unit risk estimates were nonpositive and not significantly different from zero, and the maximum (95% UCL) unit risk estimates for lung cancer were lower than those in US EPA (2010). Conclusions. These data do not demonstrate an increased risk of lung cancer associated with median drinking water arsenic levels in the range ...
Determinants of lung cancer risk among cadmium-exposed workers
Annals of Epidemiology, 1992
Workers at a cadmium recovery pIant in Globe, Colorado, showed an increased risk of lung cancer, which some investigators have attributed to cadmium exposure. We conducted a cohort mortality analysis of this work force and a case-control analysis of the lung cancer cases within this work force in order to assess the probable causes of the lung cancer excess. The Globe plant began as a lead smelter about 1886, switched to arsenic production in 1920, and became a cadmium metal production facility in 1926. Cadmium, arsenic, and cigarette smoking are three potential lung carcinogens found in this workplace. Industrial hygiene data collected from I943 onward served as the basis for the National Institute for Occupational Safety and Health (NIOSH)-derived exposure algorithm that assigned cadmium exposure estimates to employees based on their work area in the plant and calendar time. Few exposure data existed for substunces other than cadmium. Feedstock ore concentrations were used us a surrogate measure of air arsenic levels. The arsenic content of the fines used as feedstock prior to I940 was considerably higher than rhat of the fines used after 1940. Smoking histories had been obtained previously for 45% of the workers. A case-control analysis of the 25 cases of lung cancer known to have occurred among these workers through 1982 was conducted using three controls per case, matched by closest data of hire and age at hire. Porenrial causal agents for lung cancer included cadmium exposure, cigarette smoking, and arsenic exposure. Exposure variables for each case and control included estimated cumulative cadmium exposure in milligram-years per cubic meter, cigarette smoking history, and plant arsenic exposure status at the time of hire. Estimated cumuhtiwe cadmium exposures of cases and controls did not differ overall or within the date-of-hire strata. Cases were more than eight rimes more likely to have been cigarette smokers than were controls. Lung cancer risk in this workplace was more closely related to the period of hire, not to the cumulative cadmium eqosure. The period of hire appears to be a surrogate for arsenic exposure as related to feedstock. The measures used here seem to indicate that exposure to arsenic and cigarette particulates, rather than to cadmium particulates, may have caused the increased rate of lung cancer of these workers. Ann Epidemiol I992;2; 195-2 11.
Arsenic, Tobacco Smoke, and Occupation Associations of Multiple Agents with Lung and Bladder Cancer
Epidemiology (Cambridge, Mass.)
Millions of people worldwide are exposed to arsenic in drinking water, and many are likely coexposed to other agents that could substantially increase their risks of arsenic-related cancer. We performed a case-control study of multiple chemical exposures in 538 lung and bladder cancer cases and 640 controls in northern Chile, an area with formerly high drinking water arsenic concentrations. Detailed information was collected on lifetime arsenic exposure, smoking, secondhand smoke, and other known or suspected carcinogens, including asbestos, silica, and wood dust. Very high lung and bladder cancer odds ratios (ORs), and evidence of greater than additive effects, were seen in people exposed to arsenic concentrations >335 µg/L and who were tobacco smokers (OR = 16, 95% confidence interval = 6.5-40 for lung cancer; and OR = 23 [8.2-66] for bladder cancer; Rothman Synergy Indices = 4.0 [1.7-9.4] and 2.0 [0.92-4.5], respectively). Evidence of greater than additive effects were also se...
Lung Cancer Development in Primary Smelter Workers: A Nested Case-Referent Study
Journal of Occupational and Environmental Medicine, 2006
The objective of this study was to study the impact of work-related exposure to mainly arsenic and lead versus smoking in primary smelter workers developing lung cancer. Methods: In a cohort of 3979 primary smelter workers, 46 subjects had contracted respiratory malignancies. They were compared with 141 age-matched male referents by conditional logistic regression analysis. Results: Cases showed a significantly higher smoking rate as compared with referents: odds ratio (OR) ϭ 4.0; 95% confidence interval (CI) ϭ 1.6-10.1; P ϭ 0.003. When restricted to smokers (33 cases, 63 referents), the cumulative air arsenic exposure index, but not the lead exposure indices, was significantly higher among the cases: OR ϭ 1.07; 95% CI ϭ 1.02-1.11; P ϭ 0.005. Conclusions: Cumulative arsenic exposure and smoking were identified as risk factors for the development of lung cancer; lead exposure, however, was not.
Major histopathological patterns of lung cancer related to arsenic exposure in German uranium miners
International Archives of Occupational and Environmental Health, 2009
Objective The mechanisms of action of arsenic in the development of lung cancer are still not yet elucidated. Considering the relationship between arsenic and squamous cell carcinomas of the skin, we hypothesized that arsenic exposure may be more closely associated with squamous cell carcinoma of the lung. Methods A comprehensive histopathological database and a detailed job-exposure matrix developed for former German uranium miners with exposure to arsenic, radon, and quartz were analyzed to quantitatively assess the effect of arsenic regarding cell type of lung cancer. The distributions of major lung cancer cell types in 1,786 German uranium miners were associated with levels of arsenic exposure under control for the other lung carcinogens. To evaluate the arsenic effects in association with a frequent occupational lung disease in miners stratification by silicosis was performed. Results There was an arsenic-related increase of the proportion of squamous cell carcinoma of the lung but restricted to miners without silicosis. The increase was found at all levels of co-exposure to radon and quartz dust. In miners with silicosis, the proportion of adenocarcinoma increased with rising arsenic exposure. Arsenic exposure was associated with non-small cell lung cancer. Silicosis turned out as major determinant of the cell type related with arsenic. Conclusion These results indicate a cell type characteristic effect of arsenic in the development of lung cancer.