Dietary modulation of the multistage, multimechanisms of human carcinogenesis: effects on initiated stem cells and cell-cell communication.

Diet can influence the risk to cancer in both negative and positive ways. Worldwide, more than 10 million persons develop cancer annually. Diet could prevent many cancers. Carcinogenesis is a multistage, multimechanism process, consisting of "initiation," "promotion," and "progression" phases. Although diet could affect each phase, an efficacious strategy for dietary chemoprevention would be intervention during the promotion phase. The tumor-promotion process requires sustained exposure to agents that stimulate the growth and inhibition of apoptosis of initiated cells in the absence of antipromoters. Chronic inflammation has been associated with the promotion process. The mechanism affecting the promotion process appears to be the inhibition of cell-cell communication between normal and initiated cells. Most, if not all, tumor-promoting agents and conditions, reversibly, inhibit cell-cell communication, whereas antipromoters, antioxidants, and anti-inflammatory agents have been shown to ameliorate the effects of tumor promoters on cell-cell communication. Additionally, adult stem cells are hypothesized to be the target cells for initiating the carcinogenic process. A new paradigm has been presented that postulates the first function of the carcinogenic process is to block the "mortalization" of a normal, "immortal" adult stem cell rather than the induction of "immortalization" of a normal mortal cell.