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American Journal of Epidemiology 2005 161(3):260-270; doi:10.1093/aje/kwi034
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Copyright © 2005 by the Johns Hopkins Bloomberg School of Public Health

ORIGINAL CONTRIBUTIONS

Predictors of Lung Cancer among Asbestos-exposed Men in the ß-Carotene and Retinol Efficacy Trial

Mark R. Cullen1 , Matt J. Barnett2, John R. Balmes3, Brenda Cartmel1, Carrie A. Redlich1, Carl A. Brodkin4, Scott Barnhart4, Linda Rosenstock5, Gary E. Goodman2,6, Sam P. Hammar7, Mark D. Thornquist2 and Gilbert S. Omenn8,9

1 Occupational and Environmental Medicine Program and the Cancer Center, Yale University School of Medicine, New Haven, CT.
2 Fred Hutchinson Cancer Research Center, Seattle, WA.
3 Department of Medicine, University of California School of Medicine, San Francisco, CA.
4 Harborview Medical Center, Seattle, WA.
5 School of Public Health, University of California, Los Angeles, Los Angeles, CA.
6 Swedish Medical Center Cancer Institute, Seattle, WA.
7 Pathology Associates of Kitsap County/Diagnostic Specialties Laboratory, Bremerton, WA.
8 Departments of Internal Medicine and Human Genetics, University of Michigan Medical School, Ann Arbor, MI.
9 Department of Public Health, University of Michigan School of Public Health, Ann Arbor, MI.

Despite numerous published studies, debate continues regarding the risk of developing lung cancer among men exposed occupationally to asbestos, particularly those without radiographic or functional evidence of asbestosis. The ß-Carotene and Retinol Efficacy Trial (CARET), a study of vitamin supplementation for chemoprevention of lung cancer, has followed 4,060 heavily exposed US men for 9–17 years. Lung cancer incidence for 1989–2002 was analyzed using a stratified proportional hazards model. The study confirmed excessive rates of lung cancer among men with radiographic asbestosis. Comparison of study arms revealed a strong, unanticipated synergy between radiographic profusion category and the active intervention. In the large subgroup of men with normal lung parenchyma on chest radiograph at baseline, there was evidence of exposure-related lung cancer risk: Men with more than 40 years’ exposure in high-risk trades had a risk approximately fivefold higher than men with 5–10 years, after adjustment for covariates. The effect in these men was independent of study intervention arm, but pleural plaques on the baseline radiograph and abnormal baseline flow rate were strong independent predictors of subsequent lung cancer. Residual confounding by subclinical asbestosis, exposure to unmeasured lung carcinogens, or differences in smoking are unlikely to explain these observations better than a carcinogenic effect of asbestos per se.

asbestos; asbestosis; beta carotene; clinical trial [publication type]; lung neoplasms; occupational exposure; vitamin A


Abbreviations: CARET, ß-Carotene and Retinol Efficacy Trial; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ILO, International Labour Organization.


Correspondence to Dr. Mark Cullen, Department of Internal Medicine, Yale University School of Medicine, 135 College Street, Room 366, New Haven, CT 06510 (e-mail: mark.cullen{at}yale.edu).


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