American Journal of Epidemiology Vol. 155, No. 7 : 622-628
Copyright © 2002 by The Johns Hopkins University School of Hygiene and Public Health
ORIGINAL CONTRIBUTIONS |
Is Residual Confounding a Reasonable Explanation for the Apparent Protective Effects of Beta-carotene Found in Epidemiologic Studies of Lung Cancer in Smokers?
From the Department of Preventive Medicine, School of Medicine, University of Southern California, Los Angeles, CA.
Deceased.
The results of three randomized trials of beta-carotene supplementation for the prevention of lung cancer among smokers are in contradiction to a large body of epidemiologic evidence for the reduction of risk of lung cancer among smokers with higher intake and/or higher serum levels of beta-carotene. Complicating this issue are widely noted negative associations between tobacco use and intake or serum levels of beta-carotene. Although observational studies attempt to control for reported smoking histories, the accuracy of self-reported smoking is uncertain; correlations as low as 0.5 between reported and true smoking exposure are not inconsistent with studies of biomarkers of cigarette exposure. The authors developed a simple statistical model for random errors in reported smoking (relative to true tobacco exposure) and assumed a modest (inverse) relation between true tobacco exposure and serum beta-carotene. Calculations from this model, combined with a model for lung cancer contemplated by Doll and Peto (J Epidemiol Community Health 1978;78:303–13), suggest that biases in assessment of smoking exposure between smokers with low versus high beta-carotene intake may plausibly explain much or all of the observed protective effect of high beta-carotene levels. Appropriate cohort studies of lung cancer in smokers, utilizing biomarkers of smoking, are needed and are presently ongoing.
beta carotene; lung neoplasms; measurement error; smoking
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