May 21, 2003

(Journal of the National Cancer Society) -- A new study suggests that cigarette smoking and alcohol intake may reverse potential benefits that the vitamin A precursor beta-carotene has on reducing the risk of colorectal polyp recurrence. Colorectal polyps, or adenomas, are benign tumors that may develop into colorectal cancer. The new study appears in the May 21 issue of the Journal of the National Cancer Institute.

Two previous randomized trials, which included mainly cigarette smokers, found that beta-carotene supplementation was associated with an increased risk of lung cancer, particularly among those who also drank alcohol. A third randomized trial, which enrolled mostly nonsmokers, found no association between beta-carotene supplementation and risk of lung cancer, suggesting that cigarette smoking and alcohol intake were somehow associated with the adverse effects of beta-carotene.

John A. Baron, M.D., of the Dartmouth Medical School, Lebanon, N.H., and his colleagues looked at how alcohol intake or smoking might modify the effects of beta-carotene on colorectal adenoma recurrence. They examined data on 864 people who had participated in the Antioxidant Polyp Prevention Study. The participants, who were polyp-free after having had previous polyps removed, were randomly assigned to receive a placebo, beta-carotene, vitamin C plus vitamin E, or beta-carotene plus vitamins C and E. Participants completed a questionnaire about their smoking habits and alcohol intake.

Among patients who did not smoke or drink, beta-carotene supplementation was associated with a 44% decrease in the risk of colorectal adenoma recurrence. However, among participants who smoked and also drank more than one alcoholic beverage per day, beta-carotene supplementation more than doubled their risk of adenoma recurrence.

Baron and his colleagues acknowledge that although their study was randomized, alcohol intake and tobacco use were reported by the subjects themselves. "Consequently these exposures bring with them the limitations of most observational analyses, including the potential for measurement error and association with other unknown lifestyle factors," the authors write.

They say that caution must be taken in choosing interventions for large-scale use, particularly when possible interactions with lifestyle factors are not well understood.

In an accompanying editorial, Bernard Levin, M.D., of the University of Texas M. D. Anderson Cancer Center in Houston, cautions that there are potential pitfalls in using an indirect marker such as incidence of adenomatous polyps, rather than incidence of colorectal cancer, to judge the benefit of a chemoprevention agent.

"Placebo-controlled, randomized trials to suppress adenoma recurrence and thus possibly to diminish colorectal cancer incidence and mortality need to be carefully monitored and to be of sufficient duration to ensure that clinically significant adverse effects can be reliably detected," he concludes.