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Julia E. Heck,^1,2 Angeline S. Andrew,^3,4 Tracy Onega,^3,4 James R. Rigas,^3,5 Brian P. Jackson,⁶ Margaret R. Karagas,^3,4 and Eric J. Duell^1,3,4

¹International Agency for Research on Cancer, Lyon, France; ²School of Public Health and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California, USA; ³Norris Cotton Cancer Center, and ⁴Section of Biostatistics and Epidemiology, Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, New Hampshire, USA; ⁵Comprehensive Thoracic Oncology Program, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA; ⁶Department of Earth Sciences, Dartmouth College, Hanover, New Hampshire, USA

Abstract
Background: 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 population-based studies.

Key words: arsenic, bronchitis, chronic obstructive pulmonary disease, lung cancer, lung diseases, New Hampshire, pulmonary fibrosis, small-cell carcinoma, smoking, http://dx.doi.org/ [Online+2+July+2009]" rel="tag">Vermont. Environ Health Perspect 117:1718–1723 (2009) . [Online 2 July 2009]

Address correspondence to E.J. Duell, Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology, Avda Gran Via 199-203, 08907 L’Hospitalet de Llobregat, Barcelona, Spain. Telephone: 34-93-260-74-01. Fax: 34-93-260-77-87. E-mail: eduell@iconcologia.net

We thank all participants in the New England Lung Cancer Study, the study staff (S. Akacem, O. Akinbobola, and A. Swoyer) , the New Hampshire State Cancer Registry (J. Rees and B. Riddle) , and the Dartmouth-Hitchcock Tumor Registry. We also thank J. Wakefield for his assistance.

This research was supported by P20RR018787 from the National Center for Research Resources, National Institutes of Health (NIH) , and in part by P42ES007373 from the National Institute of Environmental Health Sciences, NIH.

The authors declare they have no competing financial interests.

Received 13 January 2009 ; accepted 2 July 2009.