Selenium in cancer prevention: a review of the evidence and mechanism of action

Selenium (Se) is an unusual trace element in having its own codon in mRNA that specifies its insertion into selenoproteins as selenocysteine (Sec), by means of a mechanism requiring a large Sec-insertion complex. This exacting insertion machinery for selenoprotein production has implications for our Se requirements for cancer prevention. If Se may protect against cancer, an adequate intake of Se is desirable. However, the level of intake in Europe and some parts of the world is not adequate for full expression of protective selenoproteins. The evidence for Se as a cancer preventive agent includes that from geographic, animal, prospective and intervention studies. Newly-published prospective studies on oesophageal, gastric-cardia and lung cancer have reinforced previous evidence which is particularly strong for prostate cancer. Interventions with Se have shown benefit in reducing the risk of cancer incidence and mortality in all cancers combined, and specifically in liver, prostate, colorectal and lung cancers. The effect seemed to be strongest in those with the lowest Se status. As the level of Se that appears to be required for optimal effect is higher than that previously understood to be required to maximise the activity of selenoenzymes, the question has been raised as to whether selenoproteins are involved in the anti-cancer process. However, recent evidence showing an association between Se, reduction of DNA damage and oxidative stress together with data showing an effect of selenoprotein genotype on cancer risk implies that selenoproteins are indeed implicated. The likelihood of simultaneous and consecutive effects at different cancer stages still allows an important role for anti-cancer Se metabolites such as methyl selenol formed from γ-glutamyl-selenomethyl-selenocysteine and selenomethylselenocysteine, components identified in certain plants and Se-yeast that have anti-cancer effects. There is some evidence that Se may affect not only cancer risk but also progression and metastasis. Current primary and secondary prevention trials of Se are underway in the USA including the SELECT prostate cancer trial, though a large European trial is still desirable given the likelihood of a stronger effect in populations of lower Se status