© 2004 by Oxford University Press
© 2004 Oxford University Press
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ARTICLE |
The Beta-Carotene and Retinol Efficacy Trial: Incidence of Lung Cancer and Cardiovascular Disease Mortality During 6-Year Follow-up After Stopping 
-Carotene and Retinol Supplements
Affiliations of authors: Fred Hutchinson Cancer Research Center, Seattle, WA (GEG, MDT); Swedish Cancer Institute, Seattle (GEG); Department of Medicine, University of California at San Francisco (JB); Yale School of Medicine, Yale University, New Haven, CT (MRC); UC Irvine Medical Center, Orange, CA (FLM, JHW); University of Michigan Medical School, Ann Arbor (GSO); Kaiser Permanente Center for Health Research, Portland, OR (BV).
Correspondence to: Gary E. Goodman, MD, MS, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. North, Bldg. M, M1-B514, Seattle, WA 98109 (e-mail: gary.goodman{at}swedish.org)
Background: The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the effect of daily 
-carotene (30 mg) and retinyl palmitate (25 000 IU) on the incidence of lung cancer, other cancers, and death in 18 314 participants who were at high risk for lung cancer because of a history of smoking or asbestos exposure. CARET was stopped ahead of schedule in January 1996 because participants who were randomly assigned to receive the active intervention were found to have a 28% increase in incidence of lung cancer, a 17% increase in incidence of death and a higher rate of cardiovascular disease mortality compared with participants in the placebo group. Methods: After the intervention ended, CARET participants returned the study vitamins to their study center and provided a final blood sample. They continue to be followed annually by telephone and mail self-report. Self-reported cancer endpoints were confirmed by review of pathology reports, and death endpoints were confirmed by review of death certificates. All statistical tests were two-sided. Results: With follow-up through December 31, 2001, the post-intervention relative risks of lung cancer and all-cause mortality for the active intervention group compared with the placebo group were 1.12 (95% confidence interval [CI] = 0.97 to 1.31) and 1.08 (95% CI = 0.99 to 1.17), respectively. Smoothed relative risk curves for lung cancer incidence and all-cause mortality indicated that relative risks remained above 1.0 throughout the post-intervention follow-up. By contrast, the relative risk of cardiovascular disease mortality decreased rapidly to 1.0 after the intervention was stopped. During the post-intervention phase, females had larger relative risks of lung cancer mortality (1.33 versus 1.14; P = .36), cardiovascular disease mortality (1.44 versus 0.93; P = .03), and all-cause mortality (1.37 versus 0.98; P = .001) than males. Conclusions: The previously reported adverse effects of -carotene and retinyl palmitate on lung cancer incidence and all-cause mortality in cigarette smokers and individuals with occupational exposure to asbestos persisted after drug administration was stopped although they are no longer statistically significant. Planned subgroup analyses suggest that the excess risks of lung cancer were restricted primarily to females, and cardiovascular disease mortality primarily to females and to former smokers.
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Editorial about this Article
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Reflections on the Landmark Studies of -Carotene Supplementation
- Anna J. Duffield-Lillico and Colin B. Begg
J Natl Cancer Inst 2004 96: 1729-1731.[Extract] [Full Text] [PDF]
Related Memo to the Media
- Press Release: Some Harms of Beta-Carotene Supplementation May Persist After Discontinuing Use
- Sarah L. Zielinski
J Natl Cancer Inst 2004 96: 1727.[Extract] [Full Text]
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