Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: 8/13/2011
Publication Date: 6/8/2012
Citation: Combs, G.F., Jackson, M.I. 2012. Selenium as a cancer preventive agent. In: Hatfield, D.L., Berry, M.J., Gladyshev, V.N. Selenium Its Molecular Biology and Role in Human Health. 3rd Edition. New York, NY: Springer. p. 313-323. Interpretive Summary:
Technical Abstract: Most epidemiological studies have shown inverse associations of selenium (Se) status and cancer risk. Almost all experimental animal studies have shown that supranutritional exposures of Se can reduce tumor yield. Each of the limited number of clinical intervention trials conducted to date has found Se treatment to be associated with reductions in cancer risks. The known metabolic functions of Se, which appear to be discharged by a fairly small number of selenoproteins, does not fully explain these effects, particularly those observed in response to Se-supplementation of non-deficient subjects. Emerging evidence indicates anticarcinogenic roles of at least some selenoproteins, namely, those involved in antioxidant protection (glutathione peroxidases), redox regulation (thioredoxin reductases) and hormonal regulation of metabolism (iodothyronine 5’-deiodinases). Abundant empirical evidence has shown anti-carcinogenic effects of Se in individuals with apparently full selenoenzyme expression suggests other mechanisms with relevance to non-deficient populations. Selenium compounds have been shown to be anticarcinogenic by altering gene expression, affecting DNA damage and repair, affecting cell signaling pathways, inhibiting cell proliferation, stimulating cell death by apoptosis, and inhibiting metastasis and neo-angiogenesis. These effects appear to result from underlying aspects of the metabolism of various Se-metabolites, including redox cycling of hydrogen selenide, selenomethionine selenoxide and methylselenol; modification of protein-thiols by methylselenol; and methionine mimicry by selenomethionine. It is therefore likely that Se-deprivation may increase cancer risk by compromising selenoprotein expression, and that supranutritional exposures to Se reducing cancer risk in non-deficient subjects. These hypotheses are not mutually exclusive, and it is likely that Se can function as a cancer preventive agent through both nutritional and supranutritional mechanisms.