Antioxidants in oral cancer prevention.

I present evidence in support of a chemopreventive role for the so-called antioxidant nutrients, beta-carotene and vitamin E, against oral cavity cancer. This evidence is from laboratory studies, animal model systems, epidemiologic surveys, intervention trials involving reversal of premalignant changes, and prevention of malignancies in particularly high-risk subjects. Because agents proposed for disease prevention are meant to be used widely without close medical supervision, almost any toxicity is unacceptable. beta-Carotene and vitamin E fulfill this criterion for a suitable chemopreventive agent. In several epidemiologic studies, low intakes of vitamin E, carotenoids, or both have been associated with a higher cancer risk. Smoking, a major risk factor, results in lower beta-carotene concentrations in plasma and oral mucosal cells. In several laboratory and animal model systems, beta-carotene and other antioxidant nutrients are inhibitors of oral cavity carcinogenesis. beta-Carotene and vitamin E can produce clinical regression of oral leukoplakia, a premalignant lesion for oral cancer. The design and limitations of such studies in oral leukoplakia are discussed. Cancer incidence reduction trials in high-risk groups have targeted prevention of second malignancies in patients cured of a primary oral cancer. These trials are in progress. The data thus far are supportive of a significant preventive role for these nutrients in oral cancer.