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Arsenic, Tobacco Smoke, and Occupation: Associations of Multiple Agents with Lung and Bladder Cancer

Ferreccio, Catterina; Yuan, Yan; Calle, Jacqueline; Benítez, Hugo; Parra, Roxana L.; Acevedo, Johanna; Smith, Allan H.; Liaw, Jane; Steinmaus, Craig

doi: 10.1097/EDE.0b013e31829e3e03

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.

Supplemental Digital Content is available in the text.

From the aDepartamento de Salud Pública, Universidad Católica de Chile, Santiago, Chile; bArsenic Research Group, School of Public Health, University of California, Berkeley, CA; and cHospital de Antofagasta, Antofagasta, Chile.

Supported by US National Institute of Environmental Health Sciences grants 5R01ES014032 and P42ES04705.

The authors report no conflicts of interest.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article ( This content is not peer-reviewed or copy-edited; it is the sole responsibility of the author.

Correspondence: Craig Steinmaus, University of California, School of Public Health, 50 University Hall, MC7360, Berkeley, CA 94720–7360. E-mail:

Received September 19, 2012

Accepted May 19, 2013

Copyright © 2013 Wolters Kluwer Health, Inc. All rights reserved.