| Respiratory Cancer and Inhaled Inorganic Arsenic in Copper Smelters Workers: A Linear Relationship with Cumulative Exposure that Increases with Concentration Jay H. Lubin,1 Lee E. Moore,2 Joseph F. Fraumeni Jr.,3 and Kenneth P. Cantor2 1Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA; 2Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, Rockville, Maryland, USA; 3Office of the Director, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA Abstract
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. Key words: arsenic, dose–response relationship, lung neoplasms, occupational diseases. Environ Health Perspect 116:1661–1665 (2008) . doi:10.1289/ehp.11515 available via http://dx.doi.org/ [Online 23 July 2008]
Address correspondence to J.H. Lubin, Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., Room 8042, Rockville, MD 20852 USA. Telephone: (301) 496-3357. Fax: (301) 402-0081. E-mail: lubinj@mail.nih.gov This research was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. The authors declare they have no competing financial interests. Received 27 March 2008 ; accepted 23 July 2008.
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