Cancer Causes & Control

, Volume 21, Issue 5, pp 679–687 | Cite as

Toenail selenium status and DNA repair capacity among female BRCA1 mutation carriers

  • Joanne Kotsopoulos
  • Zhou Chen
  • Katherine A. Vallis
  • Aletta Poll
  • Parviz Ghadirian
  • Greg Kennedy
  • Peter Ainsworth
  • Steven A. Narod
Original paper


Selenium is an important cofactor of various antioxidant enzymes and has been shown to enhance DNA repair in normal human fibroblasts. Oral selenium supplementation has also been shown to decrease the number of chromosome breaks in BRCA1 mutation carriers. Because the predisposition to cancer among BRCA1 mutation carriers may be linked to high rates of DNA damage and chromosome breakage, we evaluated the association between toenail selenium concentrations and three measures of DNA repair capacity (the single-cell alkaline gel electrophoresis (comet) assay, the micronucleus test, and the enumeration of γ-H2AX nuclear foci) in female BRCA1 mutation carriers and in non-carriers. Toenail selenium levels were inversely associated with levels of chromosomal damage following exposure to gamma-irradiation, as assessed by the micronucleus test. This association was limited to women with a BRCA1 mutation (p = 0.03). Toenail selenium was not a significant predictor of DNA repair capacity, as quantified by either the comet assay or the number of γ-H2AX foci, in carriers or in non-carriers. These results provide evidence for a possible protective effect of selenium against BRCA1-associated breast cancers.


Selenium BRCA1 DNA repair 



J.K. is the recipient of a Cancer Care Ontario Research Chair in Population Studies.


  1. 1.
    Scott RJ (2004) DNA double strand break repair and its association with inherited predispositions to breast cancer. Hered Cancer Clin Pract 2(1):37–43CrossRefPubMedGoogle Scholar
  2. 2.
    Bae I, Fan S, Meng Q, Rih JK, Kim HJ, Kang HJ et al (2004) BRCA1 induces antioxidant gene expression and resistance to oxidative stress. Cancer Res 64(21):7893–7909CrossRefPubMedGoogle Scholar
  3. 3.
    Kowalska E, Narod SA, Huzarski T, Zajaczek S, Huzarska J, Gorski B et al (2005) Increased rates of chromosome breakage in BRCA1 carriers are normalized by oral selenium supplementation. Cancer Epidemiol Biomarkers Prev 14(5):1302–1306CrossRefPubMedGoogle Scholar
  4. 4.
    Narod SA, Offit K (2005) Prevention and management of hereditary breast cancer. J Clin Oncol 23(8):1656–1663CrossRefPubMedGoogle Scholar
  5. 5.
    Seo YR, Sweeney C, Smith ML (2002) Selenomethionine induction of DNA repair response in human fibroblasts. Oncogene 21(23):3663–3669CrossRefPubMedGoogle Scholar
  6. 6.
    Csizmadi I, Kahle L, Ullman R, Dawe U, Zimmerman TP, Friedenreich CM et al (2007) Adaptation and evaluation of the national cancer institute’s diet history questionnaire and nutrient database for Canadian populations. Public Health Nutr 10(1):88–96CrossRefPubMedGoogle Scholar
  7. 7.
    Kotsopoulos J, Chen Z, Vallis KA, Poll A, Ainsworth P, Narod SA (2007) DNA repair capacity as a possible biomarker of breast cancer risk in female BRCA1 mutation carriers. Br J Cancer 96(1):118–125CrossRefPubMedGoogle Scholar
  8. 8.
    Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175(1):184–191CrossRefPubMedGoogle Scholar
  9. 9.
    Green MH, Lowe JE, Harcourt SA, Akinluyi P, Rowe T, Cole J et al (1992) UV-C sensitivity of unstimulated and stimulated human lymphocytes from normal and xeroderma pigmentosum donors in the comet assay: a potential diagnostic technique. Mutat Res 273(2):137–144PubMedGoogle Scholar
  10. 10.
    Olive PL, Banath JP, Durand RE (1990) Heterogeneity in radiation-induced DNA damage and repair in tumor and normal cells measured using the “comet” assay. Radiat Res 122(1):86–94CrossRefPubMedGoogle Scholar
  11. 11.
    Khan MA, Hill RP, Van Dyk J (1998) Partial volume rat lung irradiation: an evaluation of early DNA damage. Int J Radiat Oncol Biol Phys 40(2):467–476PubMedGoogle Scholar
  12. 12.
    Fenech M (2000) The in vitro micronucleus technique. Mutat Res 455(1–2):81–95PubMedGoogle Scholar
  13. 13.
    Al Rashid ST, Dellaire G, Cuddihy A, Jalali F, Vaid M, Coackley C et al (2005) Evidence for the direct binding of phosphorylated p53 to sites of DNA breaks in vivo. Cancer Res 65(23):10810–10821CrossRefPubMedGoogle Scholar
  14. 14.
    Reitsema TJ, Banath JP, MacPhail SH, Olive PL (2004) Hypertonic saline enhances expression of phosphorylated histone H2AX after irradiation. Radiat Res 161(4):402–408CrossRefPubMedGoogle Scholar
  15. 15.
    Pilch DR, Sedelnikova OA, Redon C, Celeste A, Nussenzweig A, Bonner WM (2003) Characteristics of gamma-H2AX foci at DNA double-strand breaks sites. Biochem Cell Biol 81(3):123–129CrossRefPubMedGoogle Scholar
  16. 16.
    Satia JA, King IB, Morris JS, Stratton K, White E (2006) Toenail and plasma levels as biomarkers of selenium exposure. Ann Epidemiol 16(1):53–58CrossRefPubMedGoogle Scholar
  17. 17.
    Ghadirian P, Maisonneuve P, Perret C, Kennedy G, Boyle P, Krewski D et al (2000) A case-control study of toenail selenium and cancer of the breast, colon, and prostate. Cancer Detect Prev 24(4):305–313PubMedGoogle Scholar
  18. 18.
    Kote-Jarai Z, Salmon A, Mengitsu T, Copeland M, Ardern-Jones A, Locke I et al (2006) Increased level of chromosomal damage after irradiation of lymphocytes from BRCA1 mutation carriers. Br J Cancer 4(2):308–310CrossRefGoogle Scholar
  19. 19.
    Speit G, Trenz K (2004) Chromosomal mutagen sensitivity associated with mutations in BRCA genes. Cytogenet Genome Res 104(1–4):325–332CrossRefPubMedGoogle Scholar
  20. 20.
    Barwell J, Pangon L, Georgiou A, Kesterton I, Langman C, Arden-Jones A et al (2007) Lymphocyte radiosensitivity in BRCA1 and BRCA2 mutation carriers and implications for breast cancer susceptibility. Int J Cancer 121(7):1631–1636CrossRefPubMedGoogle Scholar
  21. 21.
    Keimling M, Kaur J, Bagadi SA, Kreienberg R, Wiesmuller L, Ralhan R (2008) A sensitive test for the detection of specific DSB repair defects in primary cells from breast cancer specimens. Int J Cancer 123(3):730–736CrossRefPubMedGoogle Scholar
  22. 22.
    van ‘t Veer P, Van der Wielen RP, Kok FJ, Hermus RJ, Sturmans F (1990) Selenium in diet, blood, and toenails in relation to breast cancer: a case-control study. Am J Epidemiol 131(6):987–994PubMedGoogle Scholar
  23. 23.
    Dorgan JF, Sowell A, Swanson CA, Potischman N, Miller R, Schussler N et al (1998) Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States). Cancer Causes Control 9(1):89–97CrossRefPubMedGoogle Scholar
  24. 24.
    Hunter DJ, Morris JS, Stampfer MJ, Colditz GA, Speizer FE, Willett WC (1990) A prospective study of selenium status and breast cancer risk. JAMA 264(9):1128–1131CrossRefPubMedGoogle Scholar
  25. 25.
    Mannisto S, Alfthan G, Virtanen M, Kataja V, Uusitupa M, Pietinen P (2000) Toenail selenium and breast cancer-a case-control study in Finland. Eur J Clin Nutr 54(2):98–103CrossRefPubMedGoogle Scholar
  26. 26.
    Kotsopoulos J, Narod SA (2005) Towards a dietary prevention of hereditary breast cancer. Cancer Causes Control 16(2):125–138CrossRefPubMedGoogle Scholar
  27. 27.
    Lane DP (1992) Cancer. p53, guardian of the genome. Nature 358(6381):15–16CrossRefPubMedGoogle Scholar
  28. 28.
    Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW (1991) Participation of p53 protein in the cellular response to DNA damage. Cancer Res 51(23 Pt 1):6304–6311PubMedGoogle Scholar
  29. 29.
    Hagmar L, Stromberg U, Tinnerberg H, Mikoczy Z (2004) Epidemiological evaluation of cytogenetic biomarkers as potential surrogate end-points for cancer. IARC Sci Publ 157:207–215PubMedGoogle Scholar
  30. 30.
    Mayne ST (2003) Antioxidant nutrients and chronic disease: use of biomarkers of exposure and oxidative stress status in epidemiologic research. J Nutr 133(Suppl 3):933S–940SPubMedGoogle Scholar
  31. 31.
    Reamer DC, Veillon C (1983) A double isotope dilution method for using stable selenium isotopes in metabolic tracer studies: analysis by gas chromatography/mass spectrometry (GC/MS). J Nutr 113(4):786–792PubMedGoogle Scholar
  32. 32.
    Willett WC (1998) Nutritional Epidemiology Second Edition ed. Oxford University Press, OxfordCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Joanne Kotsopoulos
    • 1
    • 2
  • Zhou Chen
    • 3
  • Katherine A. Vallis
    • 4
  • Aletta Poll
    • 1
  • Parviz Ghadirian
    • 5
  • Greg Kennedy
    • 6
  • Peter Ainsworth
    • 7
  • Steven A. Narod
    • 1
    • 2
  1. 1.Women’s College Research InstituteTorontoCanada
  2. 2.Dalla Lana School of Public Health, University of TorontoTorontoCanada
  3. 3.Department of Radiation OncologyPrincess Margaret HospitalTorontoCanada
  4. 4.Experimental Radiation Therapeutics Group, Gray Institute For Radiation Oncology and BiologyOxfordUK
  5. 5.Epidemiology Research Unit, Research CentreCentre Hospitalier De l’Université de Montréal Hôtel-DieuMontrealCanada
  6. 6.Department of Engineering PhysicsÉcole PolytechniqueMontrealCanada
  7. 7.London Regional Program, London Health Sciences CentreLondonCanada

Personalised recommendations