Dietary nutrients can influence cancer risk by inhibiting or enhancing carcinogenesis through diverse mechanisms of action. The identification and elucidation of their sites of action have been a focus of nutrition and cancer research for more than four decades. Transforming nutrition and cancer research from a predominantly observational to a molecular approach offers exciting opportunities for truly identifying those who will and will not benefit from dietary intervention strategies. The emerging field of nutritional genomics, defined here as the study of any genetic or epigenetic interaction with a nutrient, will be key to this evolution. Unraveling which genetic upregulation or downregulation leads to subsequent phenotype changes will not be easy. There is evidence that genetic polymorphisms can influence the dynamics between nutrients and molecular targets and, thus, contribute to variation in response among individuals. Because many molecular targets will likely be identified, it may be necessary to credential nutrients, that is, to determine which specific nutrient-related genetic and epigenetic changes bring about phenotypic changes, to establish which interactions are the most important and under what circumstances. Vitamin D, calcium, folate, selenium, genistein, and resveratrol are highlighted, because they represent specific classes of nutrients and illustrate the need to credential various nutrients to understand their physiological significance in cancer prevention. As the science of nutrition unfolds, a clearer understanding will emerge about how nutrients can modulate cancer risk through molecular interactions and how foods might be changed by agronomic approaches and/or biotechnology. Undeniably, embracing new genomic technologies offers exciting opportunities for advances in the broad area of nutrition, especially those related to cancer prevention.

The selection of micronutrients, defined as essential and nonessential dietary components consumed in minute quantities, for testing in clinical chemoprevention trials is based on the totality of evidence arising from epidemiologic, in vitro, animal, and clinical studies. Those micronutrients that surface with chemopreventive potential, in terms of high efficacy and low toxicity, in early-phase clinical studies are then candidates for large-scale, randomized clinical chemoprevention trials with cancer endpoints. Micronutrients currently being examined in National Cancer Institute (NCI)-sponsored phase I, II, or III chemoprevention trials for prostate, breast, and colon cancers include isoflavones, lycopene, selenized yeast, selenomethionine, selenium, vitamin E, perillyl alcohol, folic acid, vitamin D, calcium, and curcumin. The response to micronutrients may vary not only in magnitude but also in direction. This variation and response likely depend on individual genetic polymorphisms and/or interactions among dietary components that influence absorption, metabolism, or site of action. Research priorities include investigation of possible molecular targets for micronutrients and whether genetic and epigenetic events dictate direction and magnitude of the response.

Dietary nutrients can influence cancer risk by inhibiting or enhancing carcinogenesis through diverse mechanisms of action. The identification and elucidation of their sites of action have been a focus of nutrition and cancer research for more than four decades. Transforming nutrition and cancer research from a predominantly observational to a molecular approach offers exciting opportunities for truly identifying those who will and will not benefit from dietary intervention strategies. The emerging field of nutritional genomics, defined here as the study of any genetic or epigenetic interaction with a nutrient, will be key to this evolution. Unraveling which genetic upregulation or downregulation leads to subsequent phenotype changes will not be easy. There is evidence that genetic polymorphisms can influence the dynamics between nutrients and molecular targets and, thus, contribute to variation in response among individuals. Because many molecular targets will likely be identified, it may be necessary to credential nutrients, that is, to determine which specific nutrient-related genetic and epigenetic changes bring about phenotypic changes, to establish which interactions are the most important and under what circumstances. Vitamin D, calcium, folate, selenium, genistein, and resveratrol are highlighted, because they represent specific classes of nutrients and illustrate the need to credential various nutrients to understand their physiological significance in cancer prevention. As the science of nutrition unfolds, a clearer understanding will emerge about how nutrients can modulate cancer risk through molecular interactions and how foods might be changed by agronomic approaches and/or biotechnology. Undeniably, embracing new genomic technologies offers exciting opportunities for advances in the broad area of nutrition, especially those related to cancer prevention.

BACKGROUND: Reduction of cancer risk by either preventing carcinogenesis or stopping carcinogenesis in its early stages is a logical approach for reducing the cancer burden, both for high-risk individuals and for the general population. The areas of dietary modification and chemoprevention show considerable promise as effective approaches for cancer prevention and are a focus of research efforts. RESULTS: Diet and cancer studies show that, generally, vegetables and fruits, dietary fiber, and certain nutrients seem to be protective against cancer, whereas fat, excessive calories, and alcohol seem to increase cancer risk. Chemoprevention research is closely linked to diet and cancer research and represents a logical research progression. CONCLUSIONS: Dietary epidemiologic studies have helped to identify many naturally occurring chemopreventive agents. Currently, randomized clinical prevention trials sponsored by the NCI include dietary interventions (eg, low-fat and/or high-fiber vegetables and fruits) targeting breast and colorectal cancer, chemoprevention trials using micronutrients (eg, vitamin E, calcium, vitamin D) aimed at lung and colorectal cancer, and chemoprevention trials testing the effectiveness of pharmaceutical agents (eg, tamoxifen, finasteride, aspirin) for breast, prostate, and colorectal cancer.