Hostname: page-component-848d4c4894-v5vhk Total loading time: 0 Render date: 2024-06-14T07:31:54.464Z Has data issue: false hasContentIssue false

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

Published online by Cambridge University Press:  07 March 2007

Margaret P. Rayman*
Division of Nutrition, Dietetics and Food, School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK
*Corresponding author: Dr Margaret Rayman, fax +44 1483 686481, email
Rights & Permissions [Opens in a new window]


Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

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 γ-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.

Symposium on ‘Micronutrients through the life cycle’
Copyright © The Nutrition Society 2005


Akbaraly, NT, Arnaud, J, Hininger-Favier, I, Gourlet, V, Roussel, A-M & Berr, C (2005) Selenium and mortality in the elderly: results from the EVA study Clinical Chemistry (In the Press).Google Scholar
Alberts, DS, Martinez, ME, Roe, DJ, Guillen-Rodriguez, JM, Marshall, , van Leeuwen, JB et al. (2000) Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. Phoenix Colon Cancer Prevention Physicians' Network. New England Journal of Medicine 342, 11561162 CrossRefGoogle ScholarPubMed
Allan, CB, Lacourciere, GM & Stadtman, TC (1999) Responsiveness of selenoproteins to dietary selenium. Annual Review of Nutrition 19, 116 CrossRefGoogle ScholarPubMed
Apostolou, S, Klein, JO, Mitsuuchi, Y, Shetler, JN, Poulikakos, PI, Jhanwar, SC, Kruger, WD & Testa, (2004) Growth inhibition and induction of apoptosis in mesothelioma cells by selenium and dependence on selenoprotein SEP15 genotype. Oncogene 23, 50325040 CrossRefGoogle ScholarPubMed
Arteel, GE, Briviba, K & Sies, H (1999) Protection against peroxynitrite. FEBS Letters 445, 226230 CrossRefGoogle ScholarPubMed
Behne, D, Kyriakopoulos, A, Kalcklosch, M, Weiss-Nowak, C, Pfeifer, H, Gessner, H & Hammel, C (1997) Two new selenoproteins found in the prostatic glandular epithelium and in the spermatid nuclei. Biomedical and Environmental Science 10, 340345 Google ScholarPubMed
Berry, MJ, Banu, L, Chen, YY, Mandel, SJ, Kieffer, JD, Harney, JW & Larsen, PR (1991) Recognition of UGA as a selenocysteine codon in type I deiodinase requires sequences in the 3' untranslated region. Nature 353, 273276 CrossRefGoogle ScholarPubMed
Berry, MJ, Banu, L, Harney, JW & Larsen, PR (1993) Functional characterization of the eukaryotic SECIS elements which direct selenocysteine insertion at UGA codons. The EMBO Journal 12, 33153322 CrossRefGoogle ScholarPubMed
Bjelakovic, G, Nikolova, D, Simonetti, RG & Gluud, C (2004) Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 364, 12191228 CrossRefGoogle ScholarPubMed
Blot, WJ, Li, JY, Taylor, PR, Guo, W, Dawsey, S, Wang, GQ, Yang, CS, Zheng, SF, Gail, M, Li, GY, et, al. (1993) Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. Journal of the National Cancer Institute 85, 14831492 CrossRefGoogle ScholarPubMed
Broadley, MR, Meacham, MC, Bowen, HC, Johnson, SE, White, PJ, Breward, N, Johnson, CC, Bryson, RJ, Harriman, M & Tucker, M (2006) Agronomic approaches for the enrichment of food crops with selenium Proceedings of the Nutrition Society (In the Press).Google Scholar
Brooks, JD, Metter, EJ, Chan, DW, Sokoll, LJ, Landis, P, Nelson, WG, Muller, D, Andres, R & Carter, HB (2001) Plasma selenium level before diagnosis and the risk of prostate cancer development. Journal of Urology 166, 20342038 CrossRefGoogle ScholarPubMed
Brown, KM & Arthur, (2001) Selenium, selenoproteins and human health: a review. Public Health Nutrition 4, 593599 CrossRefGoogle ScholarPubMed
Brown, KM, Pickard, K, Nicol, F, Beckett, GJ, Duthie, GG & Arthur, (2000) Effects of organic and inorganic selenium supplementation on selenoenzyme activity in blood lymphocytes, granulocytes, platelets and erythrocytes. Clinical Science (London) 98, 593599.CrossRefGoogle ScholarPubMed
Burk, RF, Hill, KE & Motley, AK (2003) Selenoprotein metabolism and function: evidence for more than one function for selenoprotein P. Journal of Nutrition 133, Suppl. 1 1517S1520S.CrossRefGoogle ScholarPubMed
CancerStats (2004a) Mortality UK. (accessed February 2004)Google Scholar
CancerStats (2004b) Cancer in the EU. (accessed November 2004)Google Scholar
Calvo, A, Xiao, N, Kang, J, Best, CJ, Leiva, I, Emmert-Buck, MR, Jorcyk, C & Green, JE (2002) Alterations in gene expression profiles during prostate cancer progression: functional correlations to tumorigenicity and down-regulation of selenoprotein-P in mouse and human tumors. Cancer Research 62, 53255335 Google ScholarPubMed
Caruso, C, Lio, D, Cavallone, L & Franceschi, C (2004) Aging, longevity, inflammation, and cancer. Annals of the New York Academy of Sciences 1028, 113 CrossRefGoogle ScholarPubMed
Clark, LC, Cantor, KP & Allaway, WH (1991) Selenium in forage crops and cancer mortality in U.S. counties. Archives of Environmental Health 46, 3742 CrossRefGoogle ScholarPubMed
Clark, LC, Combs, GF, Turnbull, BW, Slate, EH, Chalker, DK, Chow, J et al. (1996) Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. Journal of the American Medical Association 276, 19571963 CrossRefGoogle ScholarPubMed
Clark, LC, Dalkin, B, Krongrad, A, Combs, GF, Turnbull, BW, Slate, EH et al. (1998) Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. British Journal of Urology 81, 730734 CrossRefGoogle ScholarPubMed
Combs, GF (2001) Selenium in global food systems. British Journal of Nutrition 85, 517547 CrossRefGoogle ScholarPubMed
Combs, GF (2005) Current evidence and research needs to support a health claim for selenium and cancer prevention. Journal of Nutrition 135, 343347 Google ScholarPubMed
Combs, GF, Gray, WP (1998) Chemopreventive agents: selenium. Pharmacological Therapy 79, 179192 CrossRefGoogle ScholarPubMed
Combs, GF, , J Jr (2001) Selenium as a cancer preventive agent. In Selenium: Its Molecular Biology and Role in Human Health, pp. 205218 [Hatfield, DL, editors]. Dordrecht, The Netherlands: Kluwer Academic Publishers.CrossRefGoogle Scholar
Davis, CD & Finley, JW (2003) Chemical versus food forms of selenium in cancer prevention. In Functional Foods and Nutraceuticals in Cancer Prevention1, pp. 5585 [Watson, RR, editors]. Ames, IA: Iowa State Press.CrossRefGoogle Scholar
Davis, CD & Uthus, EO (2003) Dietary folate and selenium affect dimethylhydrazine-induced aberrant crypt formation, global DNA methylation and one-carbon metabolism in rats. Journal of Nutrition 133, 29072914 CrossRefGoogle ScholarPubMed
Davis, CD, Uthus, EO & Finley, JW (2000) Dietary selenium and arsenic affect DNA methylation in vitro in Caco-2 cells and in vivo in rat liver and colon. Journal of Nutrition 130, 29032909 CrossRefGoogle ScholarPubMed
Diplock, AT (1993) Indexes of selenium status in human populations. American Journal of Clinical Nutrition 57, Suppl.. 256S258S.CrossRefGoogle ScholarPubMed
Diwadkar-Navsariwala, V & Diamond, AM (2004) The link between selenium and chemoprevention: a case for selenoproteins. Journal of Nutrition 134, 28992902 CrossRefGoogle ScholarPubMed
Dong, Y, Zhang, H, Hawthorn, L, Ganther, HE & Ip, C (2003) Delineation of the molecular basis for selenium-induced growth arrest in human prostate cancer cells by oligonucleotide array. Cancer Research 63, 5259 Google ScholarPubMed
Duffield, AJ, Thomson, CD, Hill, KE & Williams, S (1999) An estimation of selenium requirements for New Zealanders. American Journal of Clinical Nutrition 70, 896903 CrossRefGoogle ScholarPubMed
Duffield-Lillico, AJ, Dalkin, BL, Reid, ME, Turnbull, BW, Slate, EH, Jacobs, ET, Marshall, & Clark, LC (2003a) Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial. British Journal of Urology 91, 608612 CrossRefGoogle ScholarPubMed
Duffield-Lillico, AJ, Reid, ME, Turnbull, BW, Combs, GF, Slate, , EH, Fischbach, LA, Marshall, Clark, LC (2002) Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the Nutritional Prevention of Cancer Trial. Cancer Epidemiology Biomarkers and Prevention 11, 630639 Google Scholar
Duffield-Lillico, AJ, Slate, E, Reid, ME, Turnbull, BW, Wilkins, PA, Combs, GF et al. (2003b) Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomised trial. Journal of the National Cancer Institute 95, 14771481 CrossRefGoogle Scholar
Fiala, ES, Staretz, ME, Pandya, GA, El-Bayoumy, K & Hamilton, SR (1998) Inhibition of DNA cytosine methyltransferase by chemopreventive selenium compounds, determined by an improved assay for DNA cytosine methyltransferase and DNA cytosine methylation. Carcinogenesis 19, 597604 CrossRefGoogle ScholarPubMed
Frausto, da, Silva, JJR & Williams, RJP (2001) The Biological Chemistry of the Elements : The Inorganic Chemistry of Life, 2nd ed. 498. Oxford Oxford: University Press.CrossRefGoogle Scholar
Ghosh, J & Myers, CE (1998) Inhibition of arachidonate 5-lipoxygenase triggers massive apoptosis in human prostate cancer cells. Proceedings of the National Academy of Sciences USA 95, 1318213187 CrossRefGoogle ScholarPubMed
Gladyshev, VN, Factor, VM, Housseau, F & Hatfield, DL (1998) Contrasting patterns of regulation of the antioxidant selenoproteins, thioredoxin reductase, and glutathione peroxidase, in cancer cells. Biochemical and Biophysical Research Communications 251, 488493 CrossRefGoogle ScholarPubMed
Goenaga, Infante, H, O'Connor, G, Rayman, M, Wahlen, R, Entwisle, J, Norris, P, Hearn, R Catterick, T (2004) Selenium speciation analysis of selenium-enriched supplements by HPLC with ultrasonic nebulisation ICP-MS and electrospray MS/MS detection. Journal of Analytical Atomic Spectrometry 19, 15291538 CrossRefGoogle Scholar
Goenaga, Infante, H, O'Connor, G, Rayman, M, Wahlen, R, Spalholz, J, Norris, P, Hearn, R Catterick, T (2005) Identification of water-soluble γ-glutamyl-CH3SeCys in yeast-based Se supplements by HPLC with ICP-MS and electrospray tandem MS. Journal of Analytical Atomic Spectrometry 20, 864870 CrossRefGoogle Scholar
Goodman, GE, Schaffer, S, Bankson, DD, Hughes, MP, Omenn, GS the Carotene and Retinol Efficacy Trial (CARET) Co-Investigators (2001) Predictors of serum in cigarette smokers and the lack of association with lung and prostate cancer risk. Cancer Epidemiology Biomarkers and Prevention 10, 10691076 Google ScholarPubMed
Gopalakrishna, R & Gundimeda, U (2002) Antioxidant regulation of protein kinase C in cancer prevention. Journal of Nutrition 132, 3819S3823S CrossRefGoogle ScholarPubMed
Greenberg, ER, Baron, JA, Tosteson, TD, Freeman, DH, Beck, GJ, Bond, JH et al. (1994) A clinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp Prevention Study Group. New England Journal of Medicine 331, 141147 CrossRefGoogle ScholarPubMed
Hatfield, DL & Gladyshev, VN (2002) How selenium has altered our understanding of the genetic code. Molecular and Cell Biology 22, 35653576 CrossRefGoogle ScholarPubMed
Helzlsouer, KJ, Huang, H-Y, Alberg, AJ, Hoffman, S, Burke, A, Norkus, EP, Morris, JS & Comstock, GW (2000) Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer. Journal of the National Cancer Institute 92, 20182023 CrossRefGoogle ScholarPubMed
Hsieh, CL, Oakley-Girvan, I, Balise, RR, Halpern, J, Gallagher, RP, Wu, AH, et, al. (2001) A Genome screen of families with multiple cases of prostate cancer: evidence of genetic heterogeneity. American Journal of Human Genetics 69, 148158 CrossRefGoogle ScholarPubMed
Hu, YJ & Diamond, AM (2003) Role of glutathione peroxidase 1 in breast cancer: loss of heterozygosity and allelic differences in the response to selenium. Cancer Research 63, 33473351 Google ScholarPubMed
Hu, YJ, Dolan, ME, Bae, R, Yee, H, Roy, M, Glickman, R, Kiremidjian-Schumacher, L & Diamond, AM (2004) Allelic loss at the GPx-1 locus in cancer of the head and neck. Biological Trace Element Research 101, 97106 CrossRefGoogle ScholarPubMed
Hu, YJ, Korotkov, KV, Mehta, R, Hatfield, DL, Rotimi, CN, Luke, A, et, al. (2001) Distribution and functional consequences of nucleotide polymorphisms in the 3'-untranslated region of the human Sep15 gene. Cancer Research 61, 23072310 Google ScholarPubMed
Ichimura, Y, Habuchi, T, Tsuchiya, N, Wang, L, Oyama, C, Sato, K, Nishiyama, H, Ogawa, O & Kato, T (2004) Increased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variant. Journal of Urology 172, 728732 CrossRefGoogle ScholarPubMed
Ip, C (1998) Lessons from basic research in selenium and cancer prevention. Journal of Nutrition 128, 18451854 CrossRefGoogle ScholarPubMed
Ip, C, Birringer, M, Block, E, Kotrebai, M, Tyson, JF, Uden, PC & Lisk, DJ (2000) Chemical speciation influences comparative activity of selenium-enriched garlic and yeast in mammary cancer prevention. Journal of Agriculture and Food Chemistry 48, 20622070 CrossRefGoogle ScholarPubMed
Ip, C, Dong, Y & Ganther, HE (2002) New concepts in selenium chemoprevention. Cancer Metastasis Reviews 21, 281289 CrossRefGoogle ScholarPubMed
Ip, C & Lisk, DJ (1997) Modulation of phase I and phase II xenobiotic-metabolizing enzymes by selenium-enriched garlic in rats. Nutrition and Cancer 28, 184188 CrossRefGoogle ScholarPubMed
Jacobs, ET, Jiang, R, Alberts, DS, Greenberg, ER, Gunter, EW, Karagas, MR, et, al. (2004) Selenium and colorectal adenoma: results of a pooled analysis. Journal of the National Cancer Institute 96, 16691675 CrossRefGoogle ScholarPubMed
Jiang, C, Ganther, H & Lu, J (2000) Monomethyl selenium-specific inhibition of MMP-2 and VEGF expression: implications for angiogenic switch regulation. Molecular Carcinogenesis 29, 236250 3.0.CO;2-E>CrossRefGoogle ScholarPubMed
Jiang, C, Jiang, W, Ip, C, Ganther, H & Lu, J (1999) Selenium-induced inhibition of angiogenesis in mammary cancer at chemopreventive levels of intake. Molecular Carcinogenesis 26, 213225 3.0.CO;2-Z>CrossRefGoogle ScholarPubMed
Jiang, C, Kim, KH, Wang, Z & Lu, J (2004) Methyl selenium-induced vascular endothelial apoptosis is executed by caspases and principally mediated by p38 MAPK pathway. Nutrition and Cancer 49, 174183 CrossRefGoogle ScholarPubMed
Jiang, C, Wang, Z, Ganther, H & Lu, J (2001) Caspases as key executors of methyl selenium-induced apoptosis (anoikis) of DU-145 prostate cancer cells. Cancer Research 61, 30623070 Google ScholarPubMed
Kaeck, M, Lu, J, Strange, R, Ip, C, Ganther, HE & Thompson, HJ (1997) Differential induction of growth arrest inducible genes by selenium compounds. Biochemical Pharmacology 53, 921926 CrossRefGoogle ScholarPubMed
Karunasinghe, N, Ryan, J, Tuckey, J, Masters, J, Jamieson, M, Clarke, LC, Marshall, JR & Ferguson, LR (2004) DNA stability and serum selenium levels in a high-risk group for prostate cancer. Cancer Epidemiology Biomarkers and Prevention 13, 391397 CrossRefGoogle Scholar
Kim, YS & Milner, J (2001) Molecular targets for selenium in cancer prevention. Nutrition and Cancer 40, 5054 CrossRefGoogle ScholarPubMed
Kiremidjian-Schumacher, L, Roy, M, Glickman, R, Schneider, K, Rothstein, S, Cooper, J, Hochster, H, Kim, M & Newman, R (2000) Selenium and immunocompetence in patients with head and neck cancer. Biological Trace Element Research 73, 97111 CrossRefGoogle ScholarPubMed
Kiremidjian-Schumacher, L, Roy, M, Wishe, HI, Cohen, MW & Stotzky, G (1994) Supplementation with selenium and human immune cell functions. Biological Trace Element Research 41, 115127 CrossRefGoogle ScholarPubMed
Klein, EA (2004) Selenium and vitamin E cancer prevention trial. Annals of the New York Academy of Sciences 1031, 234241 CrossRefGoogle ScholarPubMed
Knekt, P (2002) Selenium status and prevention of chronic diseases. In Handbook of Antioxidants, pp. 665687 [Cadenas, E, Packer, L, editors]. New York and Basel: Marcel Dekker Inc.Google Scholar
Knekt, P, Aromaa, A, Maatela, J, Alfthan, G, Aaran, RK, Hakama, M, Hakulinen, T, Peto, R & Tepo, L (1990) Serum selenium and subsequent risk of cancer among Finnish men and women. Journal of the National Cancer Institute 82, 864868 CrossRefGoogle ScholarPubMed
Knight, JA, Onay, UV, Wells, S, Li, H, Shi, EJ, Andrulis, IL & Ozcelik, H (2004) Genetic variants of GPX1 and SOD2 and breast cancer risk at the Ontario site of the Breast Cancer Family Registry. Cancer Epidemiology Biomarkers and Prevention 13, 146149 CrossRefGoogle ScholarPubMed
Kok, FJ, de Bruijn, AM, Hofman, A, Vermeeren, R & Valkenburg, HA (1987) Is serum selenium a risk factor for cancer in men only. American Journal of Epidemiology 125, 1216 CrossRefGoogle ScholarPubMed
Korotkov, KV, Kumaraswamy, E, Zhou, Y, Hatfield, DL & Gladyshev, VN (2001) Association between the 15-kDa selenoprotein and UDP-glucose:glycoprotein glucosyltransferase in the endoplasmic reticulum of mammalian cells. Journal of Biological Chemistry 276, 1533015336 CrossRefGoogle ScholarPubMed
Kotrebai, M, Birringer, M, Tyson, JF, Block, E & Uden, PC (2000) Selenium speciation in enriched and natural samples by HPLC-ICP-MS and HPLC-ESI-MS with perfluorinated carboxylic acid ion-pairing agents. Analyst 125, 7178 CrossRefGoogle ScholarPubMed
Kowalska, E, Narod, SA, Huzarski, T, Zajaczek, S, Huzarska, J, Gorski, B & Lubinski, J (2005) Increased rates of chromosome breakage in BRCA1 carriers are normalized by oral selenium supplementation. Cancer Epidemiology Biomarkers and Prevention 14, 13021306 CrossRefGoogle ScholarPubMed
Krishnaswamy, K, Prasad, MP, Krishna, TP, Annapurna, VV & Reddy, GA (1995) A case study of nutrient intervention of oral precancerous lesions in India. European Journal of Cancer 31, B4148 CrossRefGoogle Scholar
Kryukov, GV, Castellano, S, Novoselov, SV, Lobanov, AV, Zehtab, O, Guigo, R & Gladyshev, VN (2003) Characterization of mammalian selenoproteomes. Science 300, 14391443 CrossRefGoogle ScholarPubMed
Kumaraswamy, E, Malykh, A, Korotkov, KV, Kozyavkin, S, Hu, Y, Kwon, SY, et, al. (2000) Structure-expression relationships of the 15-kDa selenoprotein gene. Possible role of the protein in cancer etiology. Journal of Biological Chemistry 275, 3554035547 CrossRefGoogle ScholarPubMed
Lanfear, J, Fleming, J, Wu, L, Webster, G & Harrison, PR (1994) The selenium metabolite selenodiglutathione induces p53 and apoptosis: relevance to the chemopreventive effects of selenium. Carcinogenesis 15, 13871392 CrossRefGoogle Scholar
Li, H, Kantoff, PW, Giovannucci, E, Leitzmann, MF, Gaziano, JM, Stampfer, MJ & Ma, J (2005) Manganese superoxide dismutase polymorphism, prediagnostic antioxidant status, and risk of clinical significant prostate cancer. Cancer Research 65, 24982504 CrossRefGoogle ScholarPubMed
Li, H, Stampfer, MJ, Giovannucci, EL, Morris, JS, Willett, WC, Gaziano, JM & Ma, J (2004) A prospective study of plasma selenium levels and prostate cancer risk. Journal of the National Cancer Institute 96, 696703 CrossRefGoogle ScholarPubMed
Li, W, Zhu, Y, Yan, X, Zhang, Q, Li, X, Ni, Z, Shen, Z, Yao, H & Zhu, J (2000) The prevention of primary liver cancer by selenium in high risk populations. Zhonghua Yu Fang Yi Xue Za Zhi 34, 336338 Google ScholarPubMed
Mark, SD, Qiao, YL, Dawsey, SM, Wu, YP, Katki, H, Gunter, EW, Fraumeni, JF, Blot, , WJ, Dong, ZW, Taylor PR (2000) Prospective study of serum selenium levels and incident esophageal and gastric cancers. Journal of the National Cancer Institute 92, 17531763 CrossRefGoogle ScholarPubMed
Marshall, JR (2001) Larry Clark's legacy: randomized controlled, selenium-based prostate cancer chemoprevention trials. Nutrition and Cancer 40, 7477 CrossRefGoogle ScholarPubMed
Medina, D & Morrison, D (1988) Current ideas on selenium as a chemopreventive agent. Pathology and Immunopathology Research 7, 187199 CrossRefGoogle ScholarPubMed
Medina, D, Thompson, H, Ganther, H & Ip, C (2001) Se-methylselenocysteine: a new compound for chemoprevention of breast cancer. Nutrition and Cancer 40, 1217 CrossRefGoogle ScholarPubMed
Nakamuro, K, Nakanishi, K, Okuno, T, Hasegawa, T & Sayato, Y (1997) Comparison of methylated selenium metabolites in rats after oral administration of various selenium compounds. Japanese Journal of Toxicology and Environmental Health 43, 14821489 Google Scholar
Nomura, AM, Lee, J, Stemmermann, GN, Combs, GF (2000) Serum selenium and subsequent risk of prostate cancer. Cancer Epidemiology Biomarkers and Prevention 9, 883887 Google ScholarPubMed
Okuno, T, Motobayashi, S, Ueno, H & Nakamuro, K (2005) Purification and characterization of mouse hepatic enzyme that converts selenomethionine to methylselenol by its alpha, gamma-elimination. Biological Trace Element Research 106, 7794 CrossRefGoogle ScholarPubMed
Overvad, K (1998) Selenium and Cancer. In Role of Trace Elements for Health Promotion and Disease Prevention, pp. 141149 [Sandstrom, B, Walter, P, editors]. Basel: Karger.CrossRefGoogle Scholar
Platz, EA & Helzlsouer, KJ (2001) Selenium, zinc, and prostate cancer. Epidemiol Rev 23, 93101 CrossRefGoogle ScholarPubMed
Prasad, MP, Mukundan, MA & Krishnaswamy, K (1995) Micronuclei and carcinogen DNA adducts as intermediate end points in nutrient intervention trial of precancerous lesions in the oral cavity. European Journal of Cancer 31, B155159 CrossRefGoogle Scholar
Ratnasinghe, D, Tangrea, JA & Andersen, JA (2000) Glutathione peroxidase codon 198 polymorphism variant increases lung cancer risk. Cancer Research 60, 63816383 Google ScholarPubMed
Rayman, MP (2000) The importance of selenium to human health. Lancet 356, 233241 CrossRefGoogle ScholarPubMed
Rayman, MP (2002) The argument for increasing selenium intake. Proceedings of the Nutrition Society 61, 203215 CrossRefGoogle ScholarPubMed
Rayman, MP (2004) The use of high-selenium yeast to raise selenium status: how does it measure up. British Journal of Nutrition 92, 557573 CrossRefGoogle Scholar
Salonen, JT, Salonen, R, Lappetelainen, R, Maenpaa, P, Alfthan, G & Puska, P (1985) Risk of cancer in relation to serum concentrations of selenium and vitamins A and E: matched case-control analysis of prospective data. British Medical Journal 290, 417420 CrossRefGoogle Scholar
Schatzkin, A, Lanza, E, Corle, D, Lance, P, Iber, F, Caan, B, et, al. (2000) Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group. New England Journal of Medicine 342, 11491155 CrossRefGoogle ScholarPubMed
Schrauzer, GN, White, DA & Schneider, CJ (1977) Cancer mortality correlation studies. III. Statistical association with dietary selenium intakes. Bioinorganic Chemistry 7, 2331 CrossRefGoogle ScholarPubMed
Shamberger, RJ & Frost, DV (1969) Possible protective effect of selenium against human cancer. Canadian Medical Association Journal 100, 682 Google ScholarPubMed
Smith, ML, Lancia, JK, Mercer, TI & Ip, C (2004) Selenium compounds regulate p53 by common and distinctive mechanisms. Anticancer Research 24, 14011408 Google ScholarPubMed
Spallholz, JE, Boylan, LM & Larsen, HS (1990) Advances in understanding selenium's role in the immune system. Annals of the New York Academy of Sciences 587, 123139 CrossRefGoogle ScholarPubMed
Spallholz, JE, Palace, VP & Reid, TW (2004) Methioninase and selenomethionine but not Se-methylselenocysteine generate methylselenol and superoxide in an in vitro chemiluminescent assay: implications for the nutritional carcinostatic activity of selenoamino acids. Biochemical Pharmacology 67, 547554 CrossRefGoogle ScholarPubMed
Stratton, MS, Reid, ME, Schwartzberg, G, Minter, FE, Monroe, BK, Alberts, DS, Marshall, JR, Ahmann, FR. (2003a) Selenium and prevention of prostate cancer in high-risk men: the Negative Biopsy Study. Anticancer Drugs 14, 589594 CrossRefGoogle ScholarPubMed
Stratton, MS, Reid, ME, Schwartzberg, G, Minter, FE, Monroe, BK, Alberts, DS, Marshall, JR & Ahmann, FR (2003b) Selenium and inhibition of disease progression in men diagnosed with prostate carcinoma: study design and baseline characteristics of the ‘Watchful Waiting’ Study. Anticancer Drugs 14, 595600 CrossRefGoogle ScholarPubMed
Sunde, RA (1997) Selenium. In Handbook of Nutritionally Essential Mineral Elements, pp. 493556 [O'Dell, BL, Sunde, RA, editors]. New York: Marcel Dekker, Inc.Google Scholar
Thomson, CD, Robinson, MF, Butler, JA & Whanger, PD (1993) Long-term supplementation with selenate and selenomethionine: selenium and glutathione peroxidase ( EC in blood components of New Zealand women. British Journal of Nutrition 69, 577588 CrossRefGoogle ScholarPubMed
Unni, E, Singh, U, Ganther, HE & Sinha, R (2001) Se-methylselenocysteine activates caspase-3 in mouse mammary epithelial tumor cells in vitro. Biofactors 14, 169177 CrossRefGoogle ScholarPubMed
van den, Brandt, PA, Zeegers, MP, Bode, P Goldbohm, RA (2003) Toenail selenium levels and the subsequent risk of prostate cancer: a prospective cohort study. Cancer Epidemiology Biomarkers and Prevention 12, 866871 Google Scholar
Villette, S, Kyle, JA, Brown, KM, Pickard, K, Milne, JS, Nicol, F, Arthur, JR & Hesketh, JE (2002) A novel single nucleotide polymorphism in the 3' untranslated region of human glutathione peroxidase 4 influences lipoxygenase metabolism. Blood Cells, Molecules and Diseases 29, 174178 CrossRefGoogle ScholarPubMed
Wang, Z, Jiang, C & Lu, J (2002) Induction of caspase-mediated apoptosis and cell-cycle G1 arrest by selenium metabolite methylselenol. Molecular Carcinogenesis 34, 113120 CrossRefGoogle ScholarPubMed
Waters, DJ, Shen, S, Cooley, DM, Bostwick, DG, Qian, J, Combs, GF, Glickman, , LT, Oteham, C, Schlittler, D Morris, JS (2003) Effects of dietary selenium supplementation on DNA damage and apoptosis in canine prostate. Journal of the National Cancer Institute 95, 237244 CrossRefGoogle ScholarPubMed
Waters, DJ, Shen, S, Glickman, LT, Cooley, DM, Bostwick, DG, Qian, J, Combs, GF, Morris, JS (2005) Prostate cancer risk and DNA damage: translational significance of selenium supplementation in a canine model. Carcinogenesis 26, 12561262 CrossRefGoogle Scholar
Wei, WQ, Abnet, CC, Qiao, YL, Dawsey, SM, Dong, ZW, Sun, XD, Fan, JH, Gunter, EW, Taylor, PR & Mark, SD (2004) Prospective study of serum selenium concentrations and esophageal and gastric cardia cancer, heart disease, stroke, and total death. American Journal of Clinical Nutrition 79, 8085 CrossRefGoogle ScholarPubMed
Weingarten, M, Zalmanovici, A & Yaphe, J (2005) Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps The Cochrane Database of Systematic Reviews 2005 West Sussex John Wiley & Sons LtdCrossRefGoogle Scholar
Whanger, PD (2004) Selenium and its relationship to cancer: an update. British Journal of Nutrition 91, 1128 CrossRefGoogle ScholarPubMed
Wiklund, F, Gillanders, EM, Albertus, JA, Bergh, A, Damber, JE, Emanuelsson, M, et, al. (2003) Genome-wide scan of Swedish families with hereditary prostate cancer: Suggestive evidence of linkage at 5q11.2 and 19p13.3. The Prostate 57, 290297 CrossRefGoogle ScholarPubMed
Willett, WC, Polk, BF, Morris, JS, Stampfer, MJ, Pressel, S, Rosner, B, Taylor, JO, Schneider, K & Hames, CG (1983) Prediagnostic serum selenium and risk of cancer. Lancet 16, 130134 CrossRefGoogle Scholar
Xia, Y, Hill, KE, Byrne, DW, Xu, J & Burk, RF (2005) Effectiveness of selenium supplements in a low-selenium area of China. American Journal of Clinical Nutrition 81, 829834 CrossRefGoogle Scholar
Yoon, SO, Kim, MM & Chung, AS (2001) Inhibitory effect of selenite on invasion of HT1080 tumor cells. Journal of Biological Chemistry 276, 2008520092 CrossRefGoogle ScholarPubMed
Yoshizawa, K, Willett, WC, Morris, SJ, Stampfer, MJ, Spiegelman, D, Rimm, EB & Giovanucci, E (1998) Study of prediagnostic selenium levels in toenails and the risk of advanced prostate cancer. Journal of the National Cancer Institute 90, 12191224 CrossRefGoogle ScholarPubMed
Yu, MW, Horng, IS, Hsu, KH, Chiang, YC, Liaw, YF & Chen, CJ (1999) Plasma selenium levels and the risk of hepatocellular carcinoma among men with chronic hepatitis virus infection. American Journal of Epidemiology 150, 367374 CrossRefGoogle ScholarPubMed
Yu, SY, Zhu, YJ & Li, WG (1997) Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong. Biological Trace Element Research 56, 117124 CrossRefGoogle ScholarPubMed
Zhuo, H, Smith, AH & Steinmaus, C (2004) Selenium and lung cancer: a quantitative analysis of heterogeneity in the current epidemiological literature. Cancer Epidemiology Biomarkers and Prevention 13, 771778 CrossRefGoogle ScholarPubMed
Zu, K & Ip, C (2003) Synergy between selenium and vitamin E in apoptosis induction is associated with activation of distinctive initiator caspases in human prostate cancer cells. Cancer Research 63, 69886995 Google ScholarPubMed