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Journal ArticleDOI

Selenium and its relationship to cancer: an update.

01 Jan 2004-British Journal of Nutrition (Cambridge University Press)-Vol. 91, Iss: 1, pp 11-28
TL;DR: Even though SeMCYS was shown to be the most effective seleno-compound in the reduction of mammary tumours, it may not be the best choice for reduction of colon tumours because several mechanisms have been proposed on the mechanism whereby Se reduces tumours.
Abstract: Selenomethionine (Semet) is the major seleno-compound in cereal grains and enriched yeast whereas Se-methylselenocysteine (SeMCYS) is the major seleno-compound in Se-accumulator plants and some plants of economic importance such as garlic and broccoli exposed to excess Se. Animals can metabolize both Semet and SeMCYS. Epidemiological studies have indicated an inverse relationship between Se intake and the incidence of certain cancers. Blood or plasma levels of Se are usually lower in patients with cancer than those without this disorder, but inconsistent results have been found with toenail-Se values and the incidence of cancer. There have been eight trials with human subjects conducted on the influence of Se on cancer incidence or biomarkers, and except for one, all have shown a positive benefit of Se on cancer reduction or biomarkers of this disorder. This is consistent with about 100 small-animal studies where Se has been shown to reduce the incidence of tumours in most of these trials. Se-enriched yeast is the major form of Se used in trials with human subjects. In the mammary-tumour model, SeMCYS has been shown to be the most effective seleno-compound identified so far in reduction of tumours. Several mechanisms have been proposed on the mechanism whereby Se reduces tumours. Even though SeMCYS was shown to be the most effective seleno-compound in the reduction of mammary tumours, it may not be the most effective seleno-compound for reduction of colon tumours.

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Journal ArticleDOI
TL;DR: The crucial factor that needs to be emphasised with regard to the health effects of selenium is the inextricable U-shaped link with status; whereas additional seenium intake may benefit people with low status, those with adequate-to-high status might be affected adversely and should not take selenum supplements.

2,297 citations

Journal ArticleDOI
TL;DR: In this paper, the authors review aspects of soil science, plant physiology and genetics underpinning crop bio-fortification strategies, as well as agronomic and genetic approaches currently taken to biofortify food crops with the mineral elements most commonly lacking in human diets: iron (Fe), zinc (Zn), copper (Cu), calcium (Ca), magnesium (Mg), iodine (I) and selenium (Se).
Abstract: Summary The diets of over two-thirds of the world's population lack one or more essential mineral elements. This can be remedied through dietary diversification, mineral supplementation, food fortification, or increasing the concentrations and/or bioavailability of mineral elements in produce (biofortification). This article reviews aspects of soil science, plant physiology and genetics underpinning crop biofortification strategies, as well as agronomic and genetic approaches currently taken to biofortify food crops with the mineral elements most commonly lacking in human diets: iron (Fe), zinc (Zn), copper (Cu), calcium (Ca), magnesium (Mg), iodine (I) and selenium (Se). Two complementary approaches have been successfully adopted to increase the concentrations of bioavailable mineral elements in food crops. First, agronomic approaches optimizing the application of mineral fertilizers and/or improving the solubilization and mobilization of mineral elements in the soil have been implemented. Secondly, crops have been developed with: increased abilities to acquire mineral elements and accumulate them in edible tissues; increased concentrations of ‘promoter’ substances, such as ascorbate, β-carotene and cysteine-rich polypeptides which stimulate the absorption of essential mineral elements by the gut; and reduced concentrations of ‘antinutrients’, such as oxalate, polyphenolics or phytate, which interfere with their absorption. These approaches are addressing mineral malnutrition in humans globally.

1,677 citations


Cites background from "Selenium and its relationship to ca..."

  • ...This compound may be effective at reducing the incidence of various cancers and has a low potential for Se toxicity (Whanger, 2004; Finlay, 2007)....

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Journal ArticleDOI
TL;DR: The function of most selenoproteins is currently unknown; however, thioredoxin reductases, glutathione peroxidases and thyroid hormone deiodinases are well characterised selenobroteins involved in redox regulation of intracellular signalling, redox homeostasis and thyroid hormones metabolism.
Abstract: The requirement of the trace element selenium for life and its beneficial role in human health has been known for several decades. This is attributed to low molecular weight selenium compounds, as well as to its presence within at least 25 proteins, named selenoproteins, in the form of the amino acid selenocysteine (Sec). Incorporation of Sec into selenoproteins employs a unique mechanism that involves decoding of the UGA codon. This process requires multiple features such as the selenocysteine insertion sequence (SECIS) element and several protein factors including a specific elongation factor EFSec and the SECIS binding protein 2, SBP2. The function of most selenoproteins is currently unknown; however, thioredoxin reductases (TrxR), glutathione peroxidases (GPx) and thyroid hormone deiodinases (DIO) are well characterised selenoproteins involved in redox regulation of intracellular signalling, redox homeostasis and thyroid hormone metabolism. Recent evidence points to a role for selenium compounds as well as selenoproteins in the prevention of some forms of cancer. A number of clinical trials are either underway or being planned to examine the effects of selenium on cancer incidence. In this review we describe some of the recent progress in our understanding of the mechanism of selenoprotein synthesis, the role of selenoproteins in human health and disease and the therapeutic potential of some of these proteins.

1,095 citations


Cites background from "Selenium and its relationship to ca..."

  • ...These differences are proposed to account for selenium compounds being more effective antioxidants and more potent cancer-preventive agents than their sulphur analogues (158, 329)....

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  • ...Selenium exerts its biologic functions largely through its presence in selenoproteins; however, some low-molecularweight selenium compounds, such as methyl selenic acid, methyl-selenocysteine, and SeMet, have been found efficient as antitumorigenic agents in animal studies and in vitro models (115, 159, 329)....

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Journal ArticleDOI
01 Nov 2005
TL;DR: Current primary and secondary prevention trials of Se are underway in the USA, including the Selenium and Vitamin E Cancer Prevention Trial (SELECT) relating to prostate cancer, although a large European trial is still desirable given the likelihood of a stronger effect in populations of lower Se status.
Abstract: Se is an unusual trace element in having its own codon in mRNA that specifies its insertion into selenoproteins as selenocysteine (SeCys), by means of a mechanism requiring a large SeCys-insertion complex. This exacting insertion machinery for selenoprotein production has implications for the 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, colo-rectal and lung cancers. The effect seems to be strongest in those individuals 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 gamma-glutamyl-selenomethyl-SeCys and selenomethyl-SeCys, components identified in certain plants and Se-enriched 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 Selenium and Vitamin E Cancer Prevention Trial (SELECT) relating to prostate cancer, although a large European trial is still desirable given the likelihood of a stronger effect in populations of lower Se status.

781 citations


Cites background from "Selenium and its relationship to ca..."

  • ...…in vivo production of small-molecular-weight Se metabolites such as CH3SeH that have potent anti-cancer properties has been inferred from work carried out by a number of research groups (Ip, 1998; Jiang et al. 1999; Ip et al. 2000, 2002; Davis & Finley, 2003; Spallholz et al. 2004; Whanger, 2004)....

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  • ...…in vitro systems, have been shown to block progression of the cell cycle, induce apoptosis of cancer cells and inhibit the formation of new blood vessels, without which tumours cannot grow or metastasise (Ip, 1998; Jiang et al. 1999; Ip et al. 2000; Davis & Finley, 2003; Whanger, 2004)....

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  • ...In one such study (Schrauzer et al. 1977), inverse correlations were observed between apparent dietary Se intakes estimated from food-consumption data in twenty-seven countries and age-corrected mortality for a number of cancers, including that of the prostate....

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  • ...As SeMe-SeCys has been found to be more than twice as effective as selenomethionine in reducing mammary tumours in rats (Whanger, 2004), even these small amounts may be important....

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  • ...…form of Se, i.e. g-glutamyl-selenomethyl (SeMe)-SeCys, that is present in plants of the Brassica and Allium families (Ip et al. 2000; Kotrebai et al. 2000; Whanger, 2004) and probably accounts for the anti-tumour effects of Se-enriched broccoli and garlic (Ip et al. 2000; Davis & Finlay, 2003)....

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References
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Journal ArticleDOI
TL;DR: Selenium is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS.

3,359 citations


"Selenium and its relationship to ca..." refers background in this paper

  • ...The author is aware of at least two human trials to further evaluate the results of the US investigation: two in the USA (University of Arizona, and the SELECT trial at NCI; Klein et al. 2001)) and one planned in Europe (PRECISE; Rayman, 2000) when the money can be obtained....

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  • ...Low-Se areas have been reported in various countries in Europe, including Scotland, Denmark, Norway, Sweden, Finland, UK, Spain, Greece, Turkey and the Balkans, but there does not appear to be any areas of excess Se in these countries....

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  • ...2001)) and one planned in Europe (PRECISE; Rayman, 2000) when the money can be obtained....

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01 Jan 2001
TL;DR: The essential trace mineral, selenium, is of fundamental importance to human health as mentioned in this paper, and it is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS.
Abstract: The essential trace mineral, selenium, is of fundamental importance to human health. As a constituent of selenoproteins, selenium has structural and enzymic roles, in the latter context being best-known as an antioxidant and catalyst for the production of active thyroid hormone. Selenium is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS. It is required for sperm motility and may reduce the risk of miscarriage. Deficiency has been linked to adverse mood states. Findings have been equivocal in linking selenium to cardiovascular disease risk although other conditions involving oxidative stress and inflammation have shown benefits of a higher selenium status. An elevated selenium intake may be associated with reduced cancer risk. Large clinical trials are now planned to confirm or refute this hypothesis. In the context of these health effects, low or diminishing selenium status in some parts of the world, notably in some European countries, is giving cause for concern.

3,068 citations

Journal ArticleDOI
25 Dec 1996-JAMA
TL;DR: Results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites and require confirmation in an independent trial of appropriate design before new public health recommendations regarding seenium supplementation can be made.
Abstract: Objective. —To determine whether a nutritional supplement of selenium will decrease the incidence of cancer. Design. —A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial. Setting. —Seven dermatology clinics in the eastern United States. Patients. —A total of 1312 patients (mean age, 63 years; range, 18-80 years) with a history of basal cell or squamous cell carcinomas of the skin were randomized from 1983 through 1991. Patients were treated for a mean (SD) of 4.5 (2.8) years and had a total follow-up of 6.4 (2.0) years. Interventions. —Oral administration of 200 μg of selenium per day or placebo. Main Outcome Measures. —The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin. The secondary end points, established in 1990, were all-cause mortality and total cancer mortality, total cancer incidence, and the incidences of lung, prostate, and colorectal cancers. Results. —After a total follow-up of 8271 person-years, selenium treatment did not significantly affect the incidence of basal cell or squamous cell skin cancer. There were 377 new cases of basal cell skin cancer among patients in the selenium group and 350 cases among the control group (relative risk [RR], 1.10; 95% confidence interval [CI], 0.95-1.28), and 218 new squamous cell skin cancers in the selenium group and 190 cases among the controls (RR, 1.14; 95% CI, 0.93-1.39). Analysis of secondary end points revealed that, compared with controls, patients treated with selenium had a nonsignificant reduction in all-cause mortality (108 deaths in the selenium group and 129 deaths in the control group [RR, 0.83; 95% CI, 0.63-1.08]) and significant reductions in total cancer mortality (29 deaths in the selenium treatment group and 57 deaths in controls [RR, 0.50; 95% CI, 0.31-0.80]), total cancer incidence (77 cancers in the selenium group and 119 in controls [RR, 0.63; 95% CI, 0.47-0.85]), and incidences of lung, colorectal, and prostate cancers. Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group, the blinded phase of the trial was stopped early. No cases of selenium toxicity occurred. Conclusions. —Selenium treatment did not protect against development of basal or squamous cell carcinomas of the skin. However, results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites. These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made.

2,780 citations


"Selenium and its relationship to ca..." refers background in this paper

  • ...In a simple experimental design (double-blind, placebo-controlled trial), 1312 older US subjects with histories of basal and/ or squamous cell carcinomas of the skin were studied (Clark et al. 1996, 1998)....

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  • ...Even though Clark et al. (1996) did not observe any effect of Se on skin cancer in their study, the results strongly indicated that other types of skin disorders may be improved by Se....

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Journal ArticleDOI
30 May 2003-Science
TL;DR: This work identified selenoprotein genes in sequenced mammalian genomes by methods that rely on identification of selenocysteine insertion RNA structures, the coding potential of UGA codons, and the presence of cysteine-containing homologs.
Abstract: In the genetic code, UGA serves as a stop signal and a selenocysteine codon, but no computational methods for identifying its coding function are available. Consequently, most selenoprotein genes are misannotated. We identified selenoprotein genes in sequenced mammalian genomes by methods that rely on identification of selenocysteine insertion RNA structures, the coding potential of UGA codons, and the presence of cysteine-containing homologs. The human selenoproteome consists of 25 selenoproteins.

2,096 citations


"Selenium and its relationship to ca..." refers background in this paper

  • ...A total of twenty-five selenoproteins have been identified in eukaryotes (Gladyshev, 2001; Kryukov et al. 2003)....

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  • ...A table of the characteristic of all twenty-five selenoproteins has been assembled by Kryukov et al. (2003)....

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  • ...The selenocysteine insertion sequences (seven so far) for the various selenoproteins have been presented by Kryukov et al. (2003)....

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Journal ArticleDOI
TL;DR: Findings indicate that vitamin and mineral supplementation of the diet of Linxian adults, particularly with the combination of beta carotene, vitamin E, and selenium, may effect a reduction in cancer risk in this population.
Abstract: Background Epidemiologic evidence indicates that diets high in fruits and vegetables are associated with a reduced risk of several cancers, including cancers of the esophagus and stomach. Vitamins and minerals in these foods may contribute to the reduced cancer risk. The people of Linxian County, China, have one of the world's highest rates of esophageal/gastric cardia cancer and a persistently low intake of several micronutrients. Purpose We sought to determine if dietary supplementation with specific vitamins and minerals can lower mortality from or incidence of cancer as well as mortality from other diseases in Linxian. Methods Individuals of ages 40-69 were recruited in 1985 from four Linxian communes. Mortality and cancer incidence during March 1986-May 1991 were ascertained for 29,584 adults who received daily vitamin and mineral supplementation throughout this period. The subjects were randomly assigned to intervention groups according to a one-half replicate of a 2(4) factorial experimental design. This design enabled testing for the effects of four combinations of nutrients: (A) retinol and zinc; (B) riboflavin and niacin; (C) vitamin C and molybdenum; and (D) beta carotene, vitamin E, and selenium. Doses ranged from one to two times U.S. Recommended Daily Allowances. Results A total of 2127 deaths occurred among trial participants during the intervention period. Cancer was the leading cause of death, with 32% of all deaths due to esophageal or stomach cancer, followed by cerebrovascular disease (25%). Significantly (P = .03) lower total mortality (relative risk [RR] = 0.91; 95% confidence interval [CI] = 0.84-0.99) occurred among those receiving supplementation with beta carotene, vitamin E, and selenium. The reduction was mainly due to lower cancer rates (RR = 0.87; 95% CI = 0.75-1.00), especially stomach cancer (RR = 0.79; 95% CI = 0.64-0.99), with the reduced risk beginning to arise about 1-2 years after the start of supplementation with these vitamins and minerals. No significant effects on mortality rates from all causes were found for supplementation with retinol and zinc, riboflavin and niacin, or vitamin C and molybdenum. Patterns of cancer incidence, on the basis of 1298 cases, generally resembled those for cancer mortality. Conclusions The findings indicate that vitamin and mineral supplementation of the diet of Linxian adults, particularly with the combination of beta carotene, vitamin E, and selenium, may effect a reduction in cancer risk in this population. Implications The results on their own are not definitive, but the promising findings should stimulate further research to clarify the potential benefits of micronutrient supplements.

1,706 citations


"Selenium and its relationship to ca..." refers background or methods in this paper

  • ...This intervention trial was conducted from 1984 to 1991 in Linxian, China, a rural county in Henan Province, where the mortalities from oesophageal cancer are among the highest in the world (Blot et al. 1993)....

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  • ...In the fourth trial a total of 29 584 adults in China were used to evaluate the effects of vitamins and minerals on cancer (Blot et al. 1993)....

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