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Selenium

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Bioactive Compounds and Cancer

Part of the book series: Nutrition and Health ((NH))

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Key Points

1. Evidence is accruing that the level of intake of selenium (Se) affects the risk of cancer and may even inhibit its spread from a primary tumour. Se exists in a number of dietary forms all of which are capable of being converted to hydrogen selenide (H2Se), a crucial molecule in Se metabolism. The nutritional functions of Se are carried out by the selenoproteins which contain Se in the form of selenocysteine (Sec).

2. A number of parallel and/or consecutive mechanisms are likely to be involved in the anti-cancer effects of Se. Evidence exists for involvement of the selenoproteins, of methylated precursors that can generate methyl selenol and of redox-cycling superoxide and hydrogen peroxide generated by oxidation of hydrogen selenide, all of which have been associated with anti-cancer effects. Thus Se compounds can modify critical sulfhydryl groups to inhibit or promote tumor cell metabolism and cell transformation.

3. Selenoenzymes are involved in antioxidant protection and anti-inflammatory effects, and may enhance the cell-mediated immune response. Se compounds can cause cell cycle arrest and apoptosis, enhance DNA repair and reduce cancer cell migration. Importantly in relation to prostate cancer, Se can down-regulate the androgen receptor.

4. While there has been fairly general acceptance that a Se metabolite, methyl selenol, is a proximal anti-carcinogen at supra-nutritional doses, data linking cancer risk with the presence of selenoprotein polymorphisms and hypermethylation of promotor regions of selenoprotein genes has also implicated selenoproteins in anti-cancer effects. Numerous cohort and nested case–control studies have shown that higher Se status is associated with a lower risk of malignancies or death from cancer. However, such evidence is subject to some uncertainty owing to the effect of inflammation on plasma or serum Se concentration which can long precede the appearance of clinical symptoms.

5. Randomized clinical trials are not subject to such effects. Data from the Nutritional Prevention of Cancer randomized trial have shown a significant protective effect of supplementation with 200 μg Se/d, as high-Se yeast, on cancer incidence and mortality with the most notable effect being on prostate cancer, with lesser effects on colorectal and lung cancers. Significant effects were confined to males, were most pronounced in former smokers and in those with plasma Se < 105 μg Se/L at baseline, a level common in European populations. By contrast, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) that gave 200 μg Se/d, as selenomethionine, to men of replete Se status [serum Se 136 (range 123–150) μg /L] showed no benefit of Se supplementation over placebo. The need for further randomised trials in populations of low baseline Se status, in women, and with a lower Se dose, e.g. 100 μg Se/d, is argued. Trials with the methyl selenol precursor, Se-methylselenocysteine, also appear warranted as do trials in subjects of known selenoprotein SNP genotype, as we can no longer assume that each person’s Se requirement to reduce cancer risk is the same.

6. In the meantime, there is no justification for increasing Se intake in persons with plasma Se above around 125 μg Se/L, though a case can certainly be made that an increased intake may benefit those whose plasma Se falls below 105 μg Se/L. However, definitive guidelines on optimal intake await further research and, for individuals rather than populations, these must ultimately be genotype related.

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  1. Nutritional Sciences Division, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK

    Margaret P. Rayman DPHIL, RPHNUTR

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  1. Nutritional Science Research Group, Division of Cancer Prevention, National Institutes of Health, Executive Boulevard 6130, Rockville, 20892, Maryland, USA

    John A. Milner

  2. Nutritional and Cancer Biology, BIO5 Institute and Center for Toxicology, The University of Arizona, Tucson, 85721-0038, Arizona, USA

    Donato F. Romagnolo

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Rayman, M.P. (2010). Selenium. In: Milner, J., Romagnolo, D. (eds) Bioactive Compounds and Cancer. Nutrition and Health. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-627-6_19

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