|Combs, Jr., Gerald - Former ARS Employee|
Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: 2/12/2016
Publication Date: 10/1/2016
Citation: Combs, Jr., G.F., Yan, L. 2016. Status of selenium in cancer prevention. In: Hatfield, D.L., Berry, M.J., Gladyshev, V.N., editors. Selenium: Its Molecular Biology and Role in Human Health. Edition 4. New York, New York. Springer-Verlag. p. 321-332. doi:10.1007/978-3-319-41283-2.
Interpretive Summary: Selenium (Se), an essential mineral to both humans and livestock, is one of a few nutrients that has been extensively studied (in both human intervention trials and pre-clinical animal studies) during past decades with demonstrated cancer preventive activities. An abundance of data from animal studies of various tumor models, including breast, prostate, and colorectal cancer, show that Se affects different stages of cancer development and growth (for example, inhibiting initiation and growth of primary tumors and delaying spread of cancer cells to distant organs), and the mechanisms by which Se exerts its anticancer effects. Mechanisms behind the Se anticancer effects include inhibiting cancer-related gene expression, causing DNA damage and repair, inducing programmed cell deaths, interrupting cancer cell signal pathways, inhibiting cell growth, cancer-related blood vessel formation and cancer invasion. Large scale intervention studies in free living people show that the cancer preventive effects of supplemental Se is largely based upon the participants’ baseline Se statues. Evidence suggests that supplemental Se offers the potential of reducing cancer risk for all Se-deficient and many non-deficient adults. The best data suggest that individuals with plasma Se levels as great as 106-121 ng/mL may benefit. That would include at least 10% of Americans, most Europeans, and many other adults in other countries.
Technical Abstract: An abundance of data indicate that selenium (Se) can be antitumorigenic. Those data, mostly from controlled studies using animal tumor models and some from clinical studies in free-living people, indicate that treatment with Se in the absence of nutritional Se-deficiency, can reduce cancer risk. That the effective doses are substantially greater than those required for supporting maximal selenoprotein expression implies independent mechanisms of antitumorigenic action. We proposed a model that rationalizes the cellular and metabolic effects of supranutritional Se status with the chemical behavior of Se metabolites. According to this theory, supranutritional exposures to Se can impair tumorigenesis in a variety of ways (affecting gene expression, DNA damage and repair, cell signaling, cell proliferation, apoptosis, neo-angiogenesis and metastasis), each of which are manifestations of underlying metabolic activities of Se-metabolites in redox cycling, modifying protein-thiols, and mimicking methionine in metabolism. That these effects appear to be physiologically consequential only at supranutritional Se exposures follows from the apparently low levels of free Se-metabolites normally present in tissues. However, it is not clear that in some circumstances the same mechanisms might not also have adverse effects. The totality of available evidence would suggest that supranutritional intakes of Se can benefit all Se-deficient individuals as well as many Se-adequate ones; however, risks associated with higher Se status merit investigation.