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Fruits and Vegetables Are Associated with Lower Lung Cancer Risk Only in the Placebo Arm of the ß-Carotene and Retinol Efficacy Trial (CARET)¹

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024 [M. L. N., R. E. P., M. D. T., I. B. K., G. E. G.]; Departments of Epidemiology [R. E. P.] and Biostatistics [M. D. T.], School of Public Health and Community Medicine, University of Washington, Seattle, Washington; and Departments of Internal Medicine and Human Genetics, and School of Public Health, University of Michigan, Ann Arbor, Michigan [G. S. O.]

Despite the unexpected results from the ß-Carotene and Retinol Efficacy Trial (CARET) and similar supplementation trials showing that supplementation with ß-carotene increased, rather than decreased, lung cancer incidence, considerable interest remains in investigating how other compounds in fruits and vegetables may affect lung cancer risk. We used data from 14,120 CARET participants who completed food frequency questionnaires to examine associations of diet with lung cancer risk. After 12 years of follow-up (1989–2001), 742 participants developed lung cancer. We used Cox proportional hazards models to estimate multivariate relative risks (RRs) and 95% confidence intervals (CIs). Analyses were controlled for smoking, asbestos exposure, and other covariates. Analyses of specific botanical groups were also controlled for total fruit and vegetable intake. All models were stratified by CARET treatment arm, and all statistical tests were two-sided. Statistically significant associations of fruit and vegetable intake with lower lung cancer risk were restricted to the CARET placebo arm. The RR for highest versus lowest quintile of total fruit consumption in the placebo arm was 0.56 (95% CI, 0.39–0.81) with a two-sided P for trend = 0.003. Two specific botanical groups were associated with reduced risk of lung cancer. Compared with the lowest quintile of rosaceae fruit consumption, placebo participants in the top quintile had a RR of 0.63 (95% CI, 0.42–0.94; P for trend = 0.02); for cruciferae vegetables, the RR was 0.68 (95% CI, 0.45–1.04; P for trend = 0.01). We did not observe any statistically significant associations of fruit and vegetable intake with lung cancer risk among participants randomized to receive the CARET supplements (30 mg of ß-carotene and 25,000 IU of retinyl palmitate). This report provides evidence that plant foods have an important preventive influence in a population at high risk for lung cancer. However, persons who use ß-carotene supplements do not benefit from the protective compounds in plant foods.

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