Micronutrients as chemopreventive agents.

The concept of chemoprevention of cancer by micronutrients is based upon evidence from human epidemiology and from studies of animal carcinogenesis models for cancer-inhibiting potential of certain minerals and vitamins. These micronutrients are diverse with respect to chemical structures and physiological effects, and include calcium, selenium, carotenoids, and vitamins A, C, D and E. The dietary intake of various micronutrients has been observed to alter significantly the incidence and mortality of a variety of human cancers including those of the oesophagus, stomach, colon, breast and cervix. Studies of laboratory animal models have also provided relevant mechanistic and efficacy data on the role of specific micronutrients as well as minor non-nutrients of dietary origin in the carcinogenic process. Micronutrients and such minor non-nutrients have been found to modulate the formation and bioactivation of carcinogens, modify the promotion and progression of carcinogenesis, alter cellular and host defences, and affect cellular differentiation-ultimately leading to variations in tumour incidences. Our understanding of biochemical and biological mechanisms of carcinogenesis and of inhibition of initiation, promotion and progression by particular micronutrients-both naturally occurring forms and their synthetic analogues-has made it possible to develop strategies for clinical intervention by these agents. It is possible that intervention with individual micronutrients and minor non-nutrients, and/or with a combination of such compounds with different modes of action, will prevent, delay or reverse the process of carcinogenesis and thus reduce the incidence of and mortality due to human cancers. A number of Phase II clinical trials have been initiated with the objective of identifying and evaluating intermediate biomarkers that will be used as surrogate end points for cancer. Several surrogate end points have been standardized and validated for their specificity. The results are very encouraging.