Diet and cancer: facts and controversies.

Evidence continues to mount that dietary components are important determinants of cancer risk and tumor behavior. Although these linkages are fascinating, numerous inconsistencies are also evident in the literature. Although multifactorial, these discrepancies likely reflect variation in the ability of food constituents to reach and/or modify critical molecular targets. Genetic polymorphisms can alter the response to dietary components (nutrigenetic effect) by influencing the absorption, metabolism, or site of action. Likewise, variation in DNA methylation patterns and other epigenomic events that influence overall gene expression can influence the biological response to food components and vice versa. Fluctuations in the ability of food components to increase or depress gene expression (nutritional transcriptomic effect) may also account for some of the inconsistencies in the response to foods. Functional proteomic studies that capture all of the proteins produced by a species and link them to physiological significance within the cell will be fundamental to understanding the relationship between dietary interventions, proteome changes, and cancer. Although a bioactive food component may influence a number of key molecular events that are involved with cancer prevention, to do so it must achieve an effective concentration within the target site, be in the correct metabolic form, and bring about a change in one or more small molecular weight signals in the cellular milleau (metabolomic effects). Fundamental to assessing and evaluating the significance of the interrelationships among bioactive food components with nutrigenetics, nutritional epigenomics, nutritional transcriptomics, proteomics, and metabolomics is knowledge about the appropriate tissue/cell or surrogate to evaluate and validated biomarkers that reflect changes in each. As the era of molecular nutrition grows, a greater understanding about the role of foods and their components on cancer risk and tumor behavior will surely unfold. Such information will be critical in the development of effective preemptive approaches to reduce the cancer burden.