Antioxidant vitamins and cancer.

Cancer is the second leading cause of death in the United States as well as most developed countries. Although advances in treatment have afforded tremendous benefits to large numbers of patients, effective primary prevention measures could, in theory, have an even greater public health impact. Diet has been postulated to account for as much as 35% of all human cancers, raising the possibility that specific constituents of diet with cancer chemopreventive effects could be identified. Risk reductions of even 20-30%, which is the most likely magnitude of any protective effect of nutritional agents, could have a significant public health impact on so common and serious a disease. Antioxidant vitamins are among the constituents of diet hypothesized to exert chemopreventive effects. Antioxidant vitamins, which include beta-carotene (pro-vitamin A), vitamin E, and vitamin C, are hypothesized to decrease cancer risk by preventing tissue damage by trapping organic free radicals and/or deactivating excited oxygen molecules, a by-product of many metabolic functions. Over 100 observational epidemiologic studies have assessed the relationship of dietary antioxidant intake or blood nutrient levels with cancer risk. Such studies are not entirely consistent but provide support for the hypothesis that antioxidant vitamin intake may decrease cancer risk. However, the chief limitation of such observational studies is their inability to control for all factors associated with vitamin intake that might independently affect cancer risk. Such unknown or unmeasured confounding variables could account for all or part of any observed associations. For this reason, definitive data on the role of antioxidant vitamins and cancer can derive only from properly conducted large-scale randomized trials of sufficient sample size, dose, and duration of treatment and follow-up. Two large-scale trials have been completed, and several are currently ongoing among well-nourished populations at high risk for cancer as well as among individuals at usual risk. Over the next several years, these trials should provide clear evidence concerning the role of antioxidant vitamins in the prevention of cancer. Such data are crucial for both individual clinical decision making as well as rational public health policy.