Abstract
Selenium is an essential micronutrient for human and animals. The function of selenium has been mainly attributed to its presence in selenoproteins. Selenium was first proposed as an antitumorigenic trace element in the late 1960s, a decade later than it was identified as a nutritional essential, based on ecological associations of cancer mortality rates and crop selenium contents in the United States. Since then, a large body of scientific evidence indicated that selenium can play a role in cancer prevention. This is supported by an extraordinarily consistent body of discoveries from studies with animal tumor and cell culture models, and by some, but not all epidemiologic studies. Both inorganic and organic selenium-compounds can be antitumorigenic at doses greater than those required to support the maximal expression of the selenoenzymes that are generally regarded as discharging the nutritional effects of the element. The evidence for selenium as a cancer preventive agent includes that from geographic, animal, prospective and intervention studies. Newly-published prospective studies on oesophageal, gastic-cardia and lung cancer have reinforced previous evidence, which is particularly strong for prostate cancer. Interventions with selenium have shown benefit in reducing the risk of cancer incidence and mortality in all cancers combined, and specifically in liver, prostate, colo-rectal and lung cancers. The effect seems to be strongest in those individuals with the lowest selenium status. As the level of selenium that appears to be required for optimal effect is higher than that previously understood to be required to maximize the activity of selenoenzymes, the questions has been raised as to whether selenoproteins are involved in the anti-cancer process. However, recent evidence showing an association between selenium, 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 selenium metabolites such as methyl selenol formed from gama-glutamyl-selenomethyl-SeCys and selenomethyl-SeCys, components identified in certain plants and selenium-enriched yeast or garlic that have anti-cancer effects. Several cancer preventive mechanisms have been described and it is likely that selenium acts through multiple pathways including inhibition of cell proliferation, induction of cell apoptosis, inhibition of angiogenesis, the anti-oxidative, and anti-inflammatory effects mediated through activity of selenoenzymes. Genetic variation in selenoenzymes may modify the potential chemopreventive effect of selenium and need to be further investigated. Current primary and secondary prevention trials of selenium are underway in the USA, including the Selenium and Vitamin E Cancer Prevention Trial relating to prostate cancer. It will be important to further evaluate the potential chemopreventive effect of selenium.
