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From the Library

Based upon the significant research progress made by our group and others in better understanding the anticancer effects of the trace mineral selenium , Dr. Waters developed a course for graduate students at Purdue University, “Selenium in Health and Disease”.  The course focused on the relationship between selenium status and cancer risk, particularly the risk of prostate cancer.  Discussions addressed the issues of measurement and epidemiology, mechanisms studied using in vitro and in vivo animal models, and interventional studies with human subjects.  Students enrolled in the 3 credit hour course for the first time in the Spring 2004 semester. The following list of 39 published scientific articles highlight the important role of selenium in health and disease.

    Review Articles on Selenium in
    Health and Disease

    Rayman MP. The importance of selenium to human health.
        Lancet 2000; 356: 233-241.

        This paper provides a critical review of the role of selenium in human health and disease.

    Combs GF Jr, Gray WP. Chemopreventive agents: selenium.
        Pharmacol Ther 1998; 79: 179-192.

        The possible mechanisms by which selenium exerts anticancer effects are reviewed.

    Vinceti M, Rovesti S, Bergomi M, Vivoli G. The epidemiology of selenium     and human cancer. Tumori 2000; 86: 105-118.
        An in-depth analysis is presented linking selenium and human cancer risk based upon
        epidemiological evidence.

    Epidemiology and Measurement
    of Selenium Status--General

    Willett WC, Morris JS, Pressel S, Taylor JO, Polk FB, Stampfer MJ,
        Rosner B, Schneider K. Prediagnostic serum selenium and risk of
    Lancet 1983; 2:130-134.

        In this seminal prospective study, investigators show that low selenium status is a significant risk factor
        for subsequent cancer development.

    Knekt P, Aromaa A, Maatela J, Alfthan G, Aaran RK, Hakama M,
        Hakulinen T, Peto R, Teppo L. Serum selenium and subsequent risk
        of cancer among Finnish men and women.
    J Natl Cancer Inst 1990;
        82: 864-868.

        Low serum selenium may be a risk factor for cancer, especially among men.

    Hunter DJ, Morris JS, Chute CG, Kushner E, Colditz GA, Stampfer MJ,
        Speizer F, Willett WC. Predictors of selenium concentration in
        human toenails.
    J Am J Epidemiol 1990; 132: 114-122.

        The use of toenail selenium concentration to assess dietary selenium intake is validated.

    Van den Brandt PA, Goldbohm RA, van’t Veer P, Bode P, Hermus RJJ,
        Sturmans F. Predictors of toenail selenium levels in men and women.
        Cancer Epidemiol Biomarker Prev 1990; 2: 107-112.

        Compared to non-smokers, toenail selenium concentration in smokers is significantly lower.

    Garland M, Morris JS, Stampfer MJ, Colditz GA, Spate VL, Baskett CK,
        Rosner B, Speizer FE, Willett WC, Hunter DJ. Prospective study
        of toenail selenium levels and cancer among women.
    J Natl Cancer
        Inst 1995; 87: 497-505.

        Selenium status is not a significant risk factor for cancer in the women of the Nurses’ Health Study.

    Rudolph RE, Vaughan TL, Kristal AR, Blount PL, Lenine DS, Galipeau PC,
        Prevo LJ, Sanchez CA, Rabinovitch PS, Reid BJ. Serum selenium levels
        in relation to markers of neoplastic progression among persons
        with Barrett’s esophagus.
    J Natl Cancer Inst 2003; 95: 750-757.

        In this cross-sectional study, high serum selenium is associated with reduced risk of esophageal cancer
        in a high-risk population.

    Epidemiology Studies on the Relationship Between Selenium and Prostate Cancer

    Yoshizawa K, Willett WC, Morris JS, Stampfer MJ, Spiegelman D, Rimm
        EB, Giovannucci E. Study of prediagnostic selenium level in
        toenails and the risk of advanced prostate cancer.
    J Natl Cancer Inst
        1998; 90: 1219-1224.

        In this seminal paper, men with the lowest toenail selenium concentration have the highest risk for
        subsequent prostate cancer development.

    Helzlsouer KJ, Huang H, Alberg AJ, Hoffman S, Burke A, Norkus EP,
        Morris JS, Comstock GW. Association between a-tocopherol,
        g-tocopherol, selenium, and subsequent prostate cancer.
    J Natl
        Cancer Inst 2000; 92: 2018-2023.

        The relationship between selenium and vitamin E status and prostate cancer risk in a Washington County,
        Maryland cohort is reported.

    Brooks JD, Metter EJ, Daniel WC, Sokoll LJ, Landis P, Melson WG, Muller
        D, Andres R, Carter HB. Plasma selenium level before diagnosis
        and the risk of prostate cancer development.
    J Urol 2001; 10:

        A threshold effect between plasma selenium level and subsequent risk of prostate cancer is demonstrated
        in the Baltimore Longitudinal Study on Aging.

    Goodman GE, Schaffer S, Bankson DD, Hughes MP, Omenn GS,
        the Carotene and the Retinol Efficacy Trial (CARET)
        Co-Investigators. Predictors of serum selenium in cigarette smokers
        and the lack of association with lung and prostate cancer risk.

        Cancer Epidemiol Biomarker Prev 2001; 10: 1069-1076.

        No significant association is found between low serum selenium and risk of lung or prostate cancer
        in the CARET study.

    Vogt TM, Siegler RG, Graudbard BI, Swanson CA, Greenberg RS,
        Schoenberg JB, Swanson GM, Hayes RB, Mayne ST. Serum selenium
        and risk of prostate cancer in U.S. blacks and whites.
    Int J Cancer
        2002; 103: 664-670.

        The most detailed analysis of selenium status and prostate cancer risk in US black men is presented.

    Van den Brandt PA, Zeegers MPA, Bode P, Goldboh RA. Toenail selenium
        levels and the subsequent risk of prostate cancer: a prospective
        cohort study.
    Cancer Epidemiol Biomarker Prev 2003; 12: 866-871.

        An inverse association is reported between toenail selenium concentration and risk for prostate cancer
        in the Netherlands.

    Cellular and Molecular Anticancer Mechanisms of Selenium--General

    Samaha HS, Hamid R, El-Bayoumy K, Rao CV, Reddy BS. The role of
        apoptosis in the modulation of colon carcinogenesis by dietary fat
        and by the organoselenium compound 1,4-phenylenebis
        (methylene) selenocyanate.
    Cancer Epidemiol Biomarker Prev 1997;
        6: 699-704.

        The first in vivo evidence is presented that dietary selenium supplementation upregulates programmed
        cell death (apoptosis) within the colonic epithelium of rats.

    Ip C, Thompson HJ, Ganther HE. Selenium modulation of cell
        proliferation and cell cycle biomarkers in normal and premalignant
        cells of the rat mammary gland.
    Cancer Epidemiol Biomarker Prev
        2000; 9: 49-54.

        Different forms of selenium exert different effects on biomarkers of cell cycle and proliferation.

    Ip C, Thompson HJ, Zhu Z, Ganther HE. In vitro and in vivo studies
        of methylseleninic acid: evidence that a monomethylated selenium
        metabolite is critical for cancer chemoprevention.
    Cancer Res 2000;
        60: 2882-2886.

        Data supporting the hypothesis that low molecular weight forms of selenium may be responsible for
        the cancer preventive effects of selenium are presented.

    Yeo J, Cha S, Cho C, Kim S, Cho J, Baek W, Suh M, Kwon TK, Park J, Suh
        S. Se-methylselenocysteine induces apoptosis through caspase
        activation and bax cleavage mediated by calpain in SKOV-3 ovarian
        cancer cells.
    Cancer Letters 2002; 182: 83-92.

        This in vitro study explores the mechanisms of selenium-induced apoptosis in human ovarian cancer cells.

    Seo YR, Kelley MR, Smith ML. Selenomethionine regulation of p53 by
        a ref1-dependent redox mechanism.
    Proc Natl Acacl Sci 2002;
        99: 14548-14553.

        Compelling evidence is presented that selenium significantly modulates the repair of DNA damage.

    Hu YJ, Diamond AM. Role of glutathione peroxidase-1 in breast cancer:
        loss of heterozygosity and allelic differences in the response
        to selenium.
    Cancer Res 2003; 63: 3347-3351.

        GPX-1 polymorphisms might explain why different people respond differently to dietary selenium

    Cellular and Molecular Mechanisms

    McCormick KDL, Rao KVN. Chemoprevention of hormone-dependent
        prostate cancer in the Wistar-Unilever rat.
    Eur Urol 1999;
        35: 464-467.

        Dietary supplementation of selenomethionine has no cancer protective effect in rats
        with chemically-induced tumors.

    Jiang C, Want Z, Ganther H, Lu J. Caspases as key executors of methyl
        selenium-induced apoptosis (anoikis) of DU-145 prostate cancer
    Cancer Res 2001; 61: 3062-3070.

        The mechanisms of selenium-induced apoptosis in DU-145 human prostate cancer cells are explored
        in vitro.

    Calvo A, Xiao N, Kang J, Best CJM, Leiva I, Emmert-Buck MR, Jorcyk C,
        Green JE. Alterations in gene expression profiles during prostate
        cancer progression: functional correlations to tumorigenicity
        and down-regulation of selenoprotein-P in mouse and human
    Cancer Res 2002; 62: 5325-6335.

        Selenoprotein gene expression is characterized in the C3(1)/Tag transgenic mouse model
        of prostate cancer.

    Gasparian AV, Yao YJ, Lu J, Yemelyanov AY, Lyakh LA, Slaga TJ,
        Budunova IV. Selenium compounds inhibit I kB Kinase (IKK)
        and Nuclear Factor-KB (NF- kB) in prostate cancer cells.
    Mol Cancer
        Ther 2002; 1: 1079-1087.

        The effect of sodium selenate and methylseleninic acid on the NF-KB activation pathway are explored
        in vitro.

    Waters DJ, Shen S, Cooley DM, Bostwick DG, Qian J, Combs GF,
        Glickman LT, Oteham CO, Schlittler D, Morris JS. Effects of dietary
        selenium supplementation on DNA damage and apoptosis in canine
    J Natl Cancer Inst 2003; 95: 237-241.

        Daily supplementation of dogs with selenomethionine or high selenium yeast significantly decreases
        DNA damage and upregulates apoptosis within the aging prostate.

    Dong Y, Zhang H, Hawthorn L, Ganther HE, Ip C. Delineation of
        the molecular basis for selenium-induced growth arrest in human
        prostate cancer cells by oligonucleotide array.
    Cancer Res 2003; 63:

        The effect of selenium (methylseleninic acid) on gene expression in PC-3 human prostate cancer cells
        is studied.

    Corcoran NM, Najdovska M, Costello AJ. Inorganic selenium retards
        progression of experimental hormone refractory prostate cancer.

        J Urol 2004; 171: 907-910.

        Dietary supplementation of mice with inorganic and organic forms of selenium have differential effects
        on the progression of orthotopically implanted PC-3 cells.

    Intervention Studies--Cancer

    Blot WJ, Li J, Taylor PR, Guo W, Dawsey S, Wang G, Yang CS, Zheng S,
        Gail M, Li G, Yu Y, Liu B, Tangrea J, Sun Y, Liu F, Fraumeni JF, Zhang
        Y, Li B. Nutrition intervention trials in Linxian, China:
        supplementation with specific vitamin/mineral combinations, cancer
        incidence, and disease-specific mortality in the general population.

        J Natl Cancer Inst 1993; 85: 1483-1492.

        Daily supplementation with a combination of beta-carotene, vitamin E, and selenium significantly
        decreases overall cancer rate in the General Population Trial conducted in Linxian, China.

    Clark LC, Combs GF, Turnbull BW, Slate EH, Chalker DK, Chow J, Savis
        LS, Glover RA, Graham GF, Gross EG, Krongrad A, Lesher JL, Park
        HK, Sanders BB, Smith CL, Taylor JR. Effects of selenium
        supplementation for cancer prevention in patients with carcinoma
        of the skin.
    J Am Med Assoc 1996; 276: 1957-1963.

        Daily supplementation with high selenium yeast is associated with a significant 63% reduction
        in prostate cancer risk in the Nutritional Prevention of Cancer Trial (NPC Trial).

    Mark SD, Qiao Y, Dawsey SM, Wu Y, Katki H, Gunter EW, Fraumeni JF,
        Blot WJ, Dong Z, Taylor PR. Prospective study of serum selenium
        levels and incident esophageal and gastric cancers.
    J Natl Cancer Inst
        2000; 92: 1753-1763.

        Low serum selenium level is associated with increased risk for esophageal and stomach cancer
        in the General Population Trial conducted in Linxian, China.

    Hoque A, Albanes D, Lippman SM, Spitz MR, Taylor PR, Klein EA,
        Thompson IM, Goodman P, Stanford JL, Crowley JJ, Coltman CA,
        Santella RM. Molecular epidemiologic studies within the Selenium
        and Vitamin E Cancer Prevention Trial (SELECT).
    Cancer Causes
        Control 2001; 12: 627-633.

        This paper outlines the proposed molecular epidemiology investigations that will be conducted in a subset
        of the men participating in the SELECT prostate cancer prevention trial.

    Duffield-Lillico AJ, Reid ME, Turnbull BW, Combs GF, Slate EH, Fischbach
        LA, Marshall JR, Clark LC. Baseline characteristics and the effects
        of selenium supplementation on cancer incidence in a randomized
        clinical trial: a summary report of the nutritional prevention of cancer
    Cancer Epidemiol Biomarker Prev 2002; 11: 630-639.

        Baseline selenium concentration prior to supplementation predicts who benefits from the cancer preventive
        effects of daily selenium supplementation in the NPC Trial.

    El-Bayoumy K, Richie JP Jr, Boyiri T, Komninou D, Prokopczyk B,
        Trushin N, Kleinman W, Cox J, Pittman B, Colosimo S. Influence of
        selenium-enriched yeast supplementation on biomarkers of oxidative
        damage and hormone status in healthy adult males.

        Cancer Epidemiol Biomarker Prev 2002; 11: 1459-1465.

        Short-term dietary supplementation with high selenium yeast has no significant effect on serum androgen
        levels in men.

    The Role of Selenium in
    Non-Cancer Diseases

    Kiremidjian-Schumacher L, Roy M, Wishe HI, Cohen MW, Stotzky G.
        Supplementation with selenium and human immune cell functions.
        Biol Trace Elem Res 1994; 41: 115-127.

        Eight weeks of daily supplementaion with sodium selenite significantly increases cytotoxic T lymphocyte
        and natural killer (NK) cell activity in healthy young volunteers.

    Beck MA, Kolbeck PC, Rohr LH, Shi Q, Morris VC, Levander OA. Benign
        human enterovirus becomes virulent in selenium-deficient mice.

        J Med Virol 1994; 43: 166-170.

        Selenium status of mice significantly influences the severity of heart pathology induced by coxsackievirus

    Campa A, Shor-Posner G, Indacochea F, Zhang G, Lai H, Asthana D,
        Scott GB, Baum MK. Mortality risk in selenium-deficient
        HIV-positive children.
    J Acquir Immune Defic Syndr 1999; 20:

        Among HIV-infected children, low plasma selenium is an independent predictor of mortality.

    Kardinaal AFM, Kok FJ, Kohlmeier L, Martin-Moreno JM. Ringstad J,
        Gomez-Aracena J, Mazaev VP, Thamm M, Martin BC, Aro A, Kark
        JD, Delgado-Rodriguez M, Riemersma RA, van ‘t Veer P, Huttunen
        JK. Association between toenail selenium and risk of acute
        myocardial infarction in European men.
    Am J Epidemiol 1997; 145:

        Selenium status is not an important predictor of risk for heart attack in a prospective, multi-institutional
        study in Europe.

    Yoshizawa K, Ascherio A. Morris JS, Stampfer MJ, Giovannucci E,
        Baskett CK, Willett WC, Rimm EB. Prospective study of selenium
        levels in toenails and risk of coronary heart disease in men.
    Am J
        Epidemiol 2003; 158: 852-860.

        No significant association is shown between toenail selenium concentration and risk of coronary heart
        disease in the Health Professionals Follow-Up Study.

    Benton D, Cook R. The impact of selenium supplementation on mood.
        Biol Psychiatry 1991; 29: 1092-1098.

        In this double-blind crossover study conducted in the United Kingdom, daily selenium supplementation is
        associated with elevated mood and decreased anxiety.