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
    cancer. 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:
    1069-1076.
    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
    supplementation.



Cellular and Molecular Mechanisms
--Prostate

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
    cells. 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
    tumors. 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
    prostate. 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:
    52-59.
    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
    trial. 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
    infection.



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:
    508-513.
    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:
    373-379.
    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.