Journal Article

Is Residual Confounding a Reasonable Explanation for the Apparent Protective Effects of Beta-carotene Found in Epidemiologic Studies of Lung Cancer in Smokers?

Daniel O. Stram, Mark Huberman and Anna H. Wu

in American Journal of Epidemiology

Published on behalf of Johns Hopkins Bloomberg School of Public Health

Volume 155, issue 7, pages 622-628
Published in print April 2002 | ISSN: 0002-9262
Published online April 2002 | e-ISSN: 1476-6256 | DOI: http://dx.doi.org/10.1093/aje/155.7.622
Is Residual Confounding a Reasonable Explanation for the Apparent Protective Effects of Beta-carotene Found in Epidemiologic Studies of Lung Cancer in Smokers?

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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.

Keywords: beta carotene; lung neoplasms; measurement error; smoking

Journal Article.  5458 words. 

Subjects: Public Health and Epidemiology

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