Carotenoids and cancer: an update with emphasis on human intervention studies.

This article gives an overview of the current state of knowledge on the cancer preventive potential of carotenoids. Numerous retrospective and prospective epidemiological studies have shown that a high intake of carotenoid-rich fruits and vegetables is associated with a decreased risk of cancer at a number of common sites. For several other cancer sites, however, the epidemiological evidence is not very consistent. A number of mechanisms for the cancer preventive properties of carotenoids have been proposed. Conversion to retinol, possibly in posthepatic tissues, would allow an effect on cellular differentiation and proliferation, and on cell-to-cell communication. Antioxidant functions could prevent free radical-induced damage to cellular DNA and other macromolecules. Immunomodulatory effects could enhance immune surveillance in tumorigenesis. In addition, non-retinol-mediated effects of carotenoids on metabolism of carcinogens and cell-to-cell communication have been shown. Observational epidemiology cannot resolve whether associations are due to a specific carotenoid, or to an associated factor in fruits and vegetables, whereas interpretation of animal studies is hampered by uncertainties in extrapolation between species, more so because the metabolism of carotenoids in most animals differs notably from that in humans. Human intervention studies on biomarkers related to cancer risk and on cancer incidence are, therefore, necessary. Human intervention studies performed so far suggest that beta-carotene can affect carcinogenesis, though not at all stages and not at all cancer sites. Implications for future human intervention research are discussed.