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Selenium pp 205-217 | Cite as

Selenium as a cancer preventive agent

  • Gerald F. CombsJr.
  • Junxuan Lü

Abstract

A confluence of different types of evidence indicates that the essential nutrient selenium can affect cancer risk. Most epidemiological studies have shown inverse associations of selenium status and cancer risk; almost all experimental animal studies have shown that supranutritional exposures of selenium can reduce tumor yield; and each of the limited number of clinical intervention trials conducted to date has found selenium treatment to be associated with reductions in cancer risks. The known metabolic functions of selenium, which appear to be discharged by a fairly small and likely incomplete number of selenoproteins may not fully explain these effects. Certainly, selenoproteins may play cancer preventive roles, namely, those involved in antioxidant protection (the glutathione peroxidases), redox regulation (the thioredoxin reductases) and hormonal regulation of metabolism (iodothyronine 5′-deiodinases). However, only minimal evidence is currently available to address the question of whether selenoenzymes are, in fact, important in cancer prevention. More abundant empirical evidence has shown anti-carcinogenic effects of selenium in individuals with apparently full selenoenzyme expression. In fact, it appears that a number of selenium-metabolites (particularly, hydrogen selenide, methylselenol and, under some circumstances, selenodiglutathione) can be directly anti-carcinogenic. Therefore, while the hypothesis remains plausible that selenium-deprivation may increase cancer risk, there is strong support for the hypothesis that supranutritional exposures to selenium can reduce cancer risk. These hypotheses are not mutually exclusive, and it is likely that selenium can function as a cancer preventive agent through both nutritional and supranutritional mechanisms.

Keywords

Cancer Risk Selenium Status Reduce Cancer Risk Selenium Dioxide Hydrogen Selenide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    K Schwarz, CM Foltz 1957 J Am Chem Soc 79:3292CrossRefGoogle Scholar
  2. 2.
    RJ Shamberger, DV Frost 1969 Can Med Assn J 104:82Google Scholar
  3. 3.
    J Shamberger, CE Willis 1971 Clin Lab Sci 2:211CrossRefGoogle Scholar
  4. 4.
    GF Combs Jr, WP Gray 1998 Pharmacol Ther 79:179CrossRefGoogle Scholar
  5. 5.
    GF Combs Jr, LC Clark 1999 Nutritional Oncology D Heber, GL Blackburn, VLW Go (Eds) Academic Press, Inc New York, 215Google Scholar
  6. 6.
    KJ Helzlsouer, AJ Alberg, EP Norkus, JS Morris, SC Hoffman, GW Comstock 1996 J Nat Cancer Inst 88:32CrossRefGoogle Scholar
  7. 7.
    KJ Helzlsouer, GW Comstock, JS Morris 1989 Cancer Res 49:6144Google Scholar
  8. 8.
    FJ Kok, AM De Bruijn, A Hofman, R Vermeeren, HA Valkenburg 1987 Am J Epidemiol 125:12Google Scholar
  9. 9.
    JT Salonen, R Salonen, R Lappeteläinen, PH Mäenpää, G Alfthan, P Puska 1985 Br Med J 290:417CrossRefGoogle Scholar
  10. 10.
    J Nayini, K El-Bayoumy, S Sugie, LA Cohen, BS Reddy 1989 Carcinogen 10:509CrossRefGoogle Scholar
  11. 11.
    W Willett, B Polk, S Morris, M Stampfer, S Preissel, B Rosner, J Taylor, K Schneider, C Hames 1983 Lancet 2:130CrossRefGoogle Scholar
  12. 12.
    Van Den Brandt, R Goldbohm, P Van’t Veer, P Bode, E Dorant, R Hermus, F Sturmans 1993 J Nat Cancer Inst 85:224CrossRefGoogle Scholar
  13. 13.
    AMY Nomura, J Lee, GN Stemmernann, GF Combs Jr 2000 Cancer Epidemiol Biomarkers Prev 9:883Google Scholar
  14. 14.
    P Philipov, K Tzatchev 1988 Zentrabl Neurochir 49:344Google Scholar
  15. 15.
    K Jaskiewicz, WFO Marasas, JW Rossouw, FE Van Niekerk, EWP Heinetech 1988 Cancer 62:263CrossRefGoogle Scholar
  16. 16.
    L. Geardsson, D Brune, IGF Nordberg, PO Wester 1985 Br J Industrial Med 42:617.Google Scholar
  17. 17.
    H Miyamoto, Y. Araya, M Ito, H Isobe, H Dosaka, T Shimizu, F Kishi, I Yamamoto., H Honma, Y Kawakami 1987 Cancer 60:1159CrossRefGoogle Scholar
  18. 18.
    P Knekt, A Aromaa, J Maatela, G Alfthan, R Aaran, M Hakama, T Hakulinen, R Peto, L Teppo 1990 J Nat Cancer Inst 82:864CrossRefGoogle Scholar
  19. 19.
    T Westin, E Ahlbom, E Johansson, B Sandstrom, I Karlberg, S. Edstrom 1989 Arch Otolaryngol Head Neck Surg 115:1079CrossRefGoogle Scholar
  20. 20.
    PGJ Burney, GW Comstock, JS Morris 1989 J Clin Nutr 49:895Google Scholar
  21. 21.
    E. Glattre, Y Thomassen, SO Thoresen, T Haldorsen, PG Lund-Larsen, L Theodorsen, J. Aaseth 1989 Int J Epidemiol 18:45CrossRefGoogle Scholar
  22. 22.
    CP Caygill, K Lavery, PA Judd, MJ Hill, AT Diplock 1989 Food Addit Contam 6:359.CrossRefGoogle Scholar
  23. 23.
    P Knekt, A Aromaa, J Maatela,G Alfthan, RK Aaran, L Teppo, M Hakama 1988 Int J Cancer 42:846CrossRefGoogle Scholar
  24. 24.
    U Reinhold, H Blitz, W Bayer, KH Schmidt 1989 Acta Derm Venerol 69:132Google Scholar
  25. 25.
    K Yoshizawa, WC Willett, SJ Morris, MJ Stampfer, D Spiegelman, EB Rimm, E Gioiovannucci 1998 J Nat Cancer Inst 90:1219CrossRefGoogle Scholar
  26. 26.
    LC Clark, LJ Hixson, GF Combs Jr, ME Reid, BW Turnbull, RE Sampliner 1993 Cancer Epidemiol Biomarkers Prev 2:41Google Scholar
  27. 27.
    GF Combs Jr 1989 Nutrition and Cancer Prevention T Moon, M Micozzi (Eds) Marcel Dekker New York, 389Google Scholar
  28. 28.
    C Ip 1998 J Nutr 128:1845.Google Scholar
  29. 29.
    L Yan, JA Yee, MH McGuire, GL Graef 1997 Nutr Cancer 28:165CrossRefGoogle Scholar
  30. 30.
    L Yan, JA Yee, D Li, MH McGuire, GL Graef 1999 Anticancer Res 19:1337Google Scholar
  31. 31.
    J Ankerst, H Sjogren 1982 Int J Cancer 29:707CrossRefGoogle Scholar
  32. 32.
    R.D. Dorado, EA Porta, TM Aquino 1985 Hepatol 5:1201CrossRefGoogle Scholar
  33. 33.
    H Nakadaira, T Ishizu, M Yamamoto 1996 Cancer Lett 106:279CrossRefGoogle Scholar
  34. 34.
    JP Perchellet, NL Abney, RM Thomas, YL Guislan, EM Perchellet 1987 Cancer Res 47:477Google Scholar
  35. 35.
    LC Clark, GF Combs Jr, BW Turnbull, E Slate, D Alberts, D Abele, R Allison, J Bradshaw, D Chalker, J Chow, D Curtis, J Dalen, L Davis, R Deal, M Dellasega, R Glover, G Graham, E Gross, J Hendrix, J Herlong, F Knight, A Krongrad, J Lesher, J Moore, K Park, J Rice, A Rogers, B Sanders, B Schurman, C Smith, E Smith, J Taylor, J Woodward 1996 J Am Med Assoc 276:1957CrossRefGoogle Scholar
  36. 36.
    LC Clark, B Dalkin, A Krongrad, GF Combs Jr, BW Turnbull, EH Slate, R Witherington, JH Herlong, E Janosko, D Carpenter, C Borosso, S Falk, J Rounder 1998 Brit J Urol 81:730CrossRefGoogle Scholar
  37. 37.
    SY Yu, YJ Zhu, WG Li 1997 Biol Trace Elem Res 56:117CrossRefGoogle Scholar
  38. 38.
    JY Li, PR Taylor, B Li, WJ Blot, W Guo, S Dawsey, GQ Wang, CS Yang, SF Zheng, M Gail, GY Li, BQ Liu, J Tangrea, YH Sun, F Liu, F Fraumeni Jr, YH Zhang 1993 J Nat Cancer Inst 85:1492CrossRefGoogle Scholar
  39. 39.
    WJ Blot, JY Li, PR Taylor, W Guo, S Dawsey, GQ Wang, CS Yang, SF Zheng, M Gail, GY Li, BQ Liu, J Tangrea, YH Sun, F Liu, F Fraumeni Jr, YH Zhang, B Li 1993 Nat Cancer Inst 85:1483CrossRefGoogle Scholar
  40. 40.
    KE Burke, GF Combs Jr, EG Gross, KC Bhuyan, H Abu-Libdeh 1992 Nutr Cancer 17:123CrossRefGoogle Scholar
  41. 41.
    BC Pence, E Pelier, DM Dunn 1994 J Invest Dermatol 102:759CrossRefGoogle Scholar
  42. 42.
    AM Diamond, P Dale, JL Murray, DJ Grdina 1996 Mutat Res 356:147CrossRefGoogle Scholar
  43. 43.
    Y Kise, M Yamamura, M Kogata, M Nakagawa, S Uetsuji, H Takada, K Hioki, M Yamamoto 1991 Nutr Cancer 16:153CrossRefGoogle Scholar
  44. 44.
    GF Combs Jr, LC Clark, BW Turnbull 2001 Proc 7 th Internat Symp Selenium Biol Med (In press)Google Scholar
  45. 45.
    J Nève 1995 J. Trace Elements Med Biol 9:65–73CrossRefGoogle Scholar
  46. 46.
    Panel on Dietary Antioxidants and Related Compounds 2000 Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium and Beta-Carotene and other Carotenoids National Academy Press Washington, D.C.Google Scholar
  47. 47.
    M Berggren, A Gallegos, JR Gasdaska, PY Gasdaskya, J Warneke, G Powis 1996 Anticancer Res 16:3459Google Scholar
  48. 48.
    G Powis, DL Kirkpatrick, M Angulo, JR Gasdaska, MB Powell, SE Salmon, WR Montfort 1996 Anticancer Drugs 7(suppl 3):121Google Scholar
  49. 49.
    QA Sun, Y Wu, F Zappacosta, KT Jeang, BJ Lee, DL Hatfield, VN Gladyshev 1999 J Biol Chem 35:24522CrossRefGoogle Scholar
  50. 50.
    MT Leccia, MJ Richard, JC Beani, H Faure, AM Monjo, J Cadet, P Amblard, A Favier 1993 Photochem Photobiol 58:548CrossRefGoogle Scholar
  51. 51.
    A Moysan, P Morliere, I Marquis, A Richard, L Dubertret 1995 Skin Pharmacol 8:139.CrossRefGoogle Scholar
  52. 52.
    CJ Bertling, F Lin, AW Girotti 1996 Photochem Photobiol 64:13CrossRefGoogle Scholar
  53. 53.
    N Emonet, MT Leccia, A Favier, JC Beani, MJ Richard 1997 J Photochem Photobiol B 40:84CrossRefGoogle Scholar
  54. 54.
    H Vorherr 1987 Eur J Cancer Clin Oncol 23:255CrossRefGoogle Scholar
  55. 55.
    P Mustacchi, FS Greenspan 1986 Wesner’s The Thyroid SH Ingbar, LE Braverman (Eds) Lippincott Philadelphia, 1453Google Scholar
  56. 56.
    JJ Strain, E Bokje, P Van’t Veer, J Coulter, C Stewart, H Logan, W Odling-Smee, RAJ Spence, K Steele 1977 Nutr Cancer 27:48CrossRefGoogle Scholar
  57. 57.
    DP Rose, TE Davis 1978 Cancer 41:666CrossRefGoogle Scholar
  58. 58.
    DP Rose, TE Davis 1979 Cancer 43:1434CrossRefGoogle Scholar
  59. 59.
    M Lemaire, L Baugnet-Mahieu 1986 Eur J Cancer Clin Oncol 22:301CrossRefGoogle Scholar
  60. 60.
    B Rasmussen, U Freedt-Rasmussen, L Hededüs, H Perrild, K Bech 1987 Eur J Cancer Clin Oncol 23:553CrossRefGoogle Scholar
  61. 61.
    O Takatani, T Okumoto, H Kosana, M Nishidi, M Hiruide 1989 Cancer Res 49:3109Google Scholar
  62. 62.
    LN Vernie 1987 Proc 3rd Internat Symp Selenium Biol Med GF Combs Jr, JE Spallholz, OA Levander, JE Oldfield (Eds) AVI Publ Co Westport, CT 1074Google Scholar
  63. 63.
    G Spyrou, M Bjornstedt, S Skog, A Holmgren 1996 Cancer Res 56:4407Google Scholar
  64. 64.
    M Bjornstedt, S Kumar, A Holmgren 1992 J Biol Chem 267:8030Google Scholar
  65. 65.
    L Wu, J Lanfear, PR Harrison 1995 Carcinogenesis 16:1579CrossRefGoogle Scholar
  66. 66.
    M Bjornstedt, S Kumar, L Bjorkhem, G Spyrou, A Holmgren 1997 Biomed Environ Sci 10:271Google Scholar
  67. 67.
    LN Vernie, CJ Hamburg, WS Bont 1981 Cancer Lett 14:303CrossRefGoogle Scholar
  68. 68.
    J Lanfear, JJ Flemming, L Wu, G Webster, PR Harrison 1994 Carcinogenesis 15:1387CrossRefGoogle Scholar
  69. 69.
    BC Pence, M Stewart, L Walsh, G Cameron 1996 Proc 6th Internat Symp Selenium Biol Med ILSI, Beijing 82Google Scholar
  70. 70.
    KA Poirier, JA Milner 1983 J Nutr 113:2147Google Scholar
  71. 71.
    PR Harrison, J Lanfear, L Wu, J Fleming, L McGarry, L Blower 1997 Biomed Environ Sci 10:235Google Scholar
  72. 72.
    J Lü, M Kaeck, C Jiang, AC Wilson, HJ Thompson 1994 Biochem Pharmacol 47:1531CrossRefGoogle Scholar
  73. 73.
    Z Zhu, M Kimura, Y Itokawa, T Aoki, JA Takahasi, S Nakatsu, Y Oda, H Kikuchi 1996 Biol Trace Elem Res 54:123CrossRefGoogle Scholar
  74. 74.
    C Ip, H Ganther 1990 Cancer Res 50:1206Google Scholar
  75. 75.
    C Ip, H Ganther 1991 Carcinogenesis 12:365CrossRefGoogle Scholar
  76. 76.
    C Ip, HE Ganther 1992 Carcinogenesis 13:1167CrossRefGoogle Scholar
  77. 77.
    C Ip, HE Ganther 1992 J Inorgan Biochem 46:215CrossRefGoogle Scholar
  78. 78.
    C Ip, C Hayes, RM Budnick, HE Ganther 1991 Cancer Res 51:595Google Scholar
  79. 79.
    S Vanhanavikit, C Ip, HE Ganther 1993 Xenobiotica 23:731CrossRefGoogle Scholar
  80. 80.
    J Lü, C Jiang, M Kaeck, H Ganther, S Vadhanavikit, C Ip, HJ Thompson 1995 Biochem Pharmacol 252:739Google Scholar
  81. 81.
    J Lü, Pei, C Ip, D Lisk, H Ganther, HJ Thompson 1996 Carcinogenesis 17:1903CrossRefGoogle Scholar
  82. 82.
    M Kaeck, J Lü, R Strange, C Ip, HE Ganther, HJ Thompson 1997 Biochem Pharmacol 53:921CrossRefGoogle Scholar
  83. 83.
    R Sinha, D Medina 1997 Carcinogenesis 18:1541CrossRefGoogle Scholar
  84. 84.
    R Sinha, SC Kiley, JX Lü, R Moraes, HJ Thompson, S Jaken, D Medina 1999 Cancer Lett 146:135CrossRefGoogle Scholar
  85. 85.
    AC Wilson, HJ Thompson, PJ Schedin, NW Gibson, HE Ganther 1992 Biochem Pharmacol 43:1137CrossRefGoogle Scholar
  86. 86.
    MS Stewart, RL Davis, LP Walsh, BC Pence 1997 Cancer Lett 117:35CrossRefGoogle Scholar
  87. 87.
    C Jiang, W Jiang, C Ip, H Ganther, J. Lü 1999 Mol Carcinogenesis 26(4):213CrossRefGoogle Scholar
  88. 88.
    C Ip, G White 1987 Carcinogenesis 8:1763CrossRefGoogle Scholar
  89. 89.
    C Ip, C Hayes 1989 Carcinogenesis 10:921CrossRefGoogle Scholar
  90. 90.
    HJ Thompson, C Ip 1991 Biol Trace Elem Res 30:163CrossRefGoogle Scholar
  91. 91.
    B Siwek, E Bahbouth, MA Serra, E Sabbioni, MC De Pauw-Gillet, R Bassleer 1994 Arch Toxicol 68:246CrossRefGoogle Scholar
  92. 92.
    C Ip, S Vadhanavkit, H Ganther 1995 Carcinogenesis 16:35CrossRefGoogle Scholar
  93. 93.
    C Ip, Z Zhu, HJ Thompson, D Lisk, HE Ganther 2000 Anticancer Res 19 (In press)Google Scholar
  94. 94.
    BS Reddy, S Sugie, H Maruyama, K El-Bayoumy, P Marra 1987 Cancer Res 47:5901Google Scholar
  95. 95.
    Z Ronai, JK Tillotson, F Traganos, Z Darzynkiewice, CC Conaway, P Upadhyaya, K El-Bayoumy 1995 Int N Cancer 63:428CrossRefGoogle Scholar
  96. 96.
    V Adler, MR Pincus, S Posner, P Upadhyay, K El-Bayoumy, Z. Ronai 1996 Carcinogenesis 17:1849CrossRefGoogle Scholar
  97. 97.
    B Prokopczyk, JE Cox, P Upadhyaya, S Amin, D Desai, D Hoffmann, K El-Bayoumy 1996 Carcinogenesis 17:749CrossRefGoogle Scholar
  98. 98.
    C Ip, H Ganther 1993 Selenium in Biology and Human Health RF Burk (Ed) Springer-Verlag New York 170Google Scholar
  99. 99.
    C Ip, K El-Bayoumy, P Upadhyaya, H Ganther, S Vadanavikit, H Thompson 1994 Carcinogenesis 15:187CrossRefGoogle Scholar
  100. 100.
    BS Reddy, A Rivenson, K El-Bayoumy, P Upadhyaya, B Pittman, CV Rao 1997 J Nat Cancer Inst 89:506CrossRefGoogle Scholar
  101. 101.
    C Ip, H Thompson, HE Ganther 1994 Carcinogenesis 15:2879CrossRefGoogle Scholar
  102. 102.
    C Ip, HJ Thompson, HE Ganther 1998 Anticancer Res 18:9Google Scholar
  103. 103.
    HE Ganther 1999 Carcinogenesis 20:1657CrossRefGoogle Scholar
  104. 104.
    HE Ganther, C Corcoran 1969 Biochem 8:2557CrossRefGoogle Scholar
  105. 105.
    PL Bergad, WB Rathbun 1986 Curr Eye Res 5:919CrossRefGoogle Scholar
  106. 106.
    R Gopalakrishna, U Gundimeda, ZH Chen 1997 Arch Biochem Biophys 348:25CrossRefGoogle Scholar
  107. 107.
    R Gopalakrishna, ZH Chen, AU Gundimed 1997 Arch Biochem Biophys 348:37CrossRefGoogle Scholar
  108. 108.
    J Chaudiere, O Courtin, J Leclaire 1992 Arch Biochem Biophys 296:328CrossRefGoogle Scholar
  109. 109.
    JE Spallholz 1997 Biomed Environ Sci 10:260Google Scholar
  110. 110.
    MS Stewart, JE Spallholz, KH Neidner, BC Pence 2000 Free Radic Biol Med 26:42CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Gerald F. CombsJr.
    • 1
  • Junxuan Lü
    • 2
  1. 1.Division of Nutritional SciencesCornell UniversityIthacaUSA
  2. 2.AMC Cancer CenterDenverUSA

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