Medical Oncology

, Volume 28, Issue 3, pp 733–737 | Cite as

Importance of ATM gene as a susceptible trait: predisposition role of D1853N polymorphism in breast cancer

  • Parvin MehdipourEmail author
  • Marzieh Mahdavi
  • Javad Mohammadi-Asl
  • Morteza Atri
Original Paper


The involvement of ATM gene and specifically, the important role of D1853N polymorphism, as a three-hit hypothesis has been previously reported in an Iranian proband affected with brain tumor and this polymorphism could be screened in her relatives as well. The aim of present study was to investigate the involvement of D1853N polymorphism as a predisposition factor in 129 Iranian patients affected with primary breast cancer and 248 sex- and age-matched healthy controls. Mutant allele-specific PCR amplification (MASA) assay was performed to analyze the D1853N polymorphism in the ATM gene. The frequency of D1853N polymorphism in cases, internal and external controls was 31.0% (40/129), 26.9% (28/104) and 12.5% (18/144), respectively. The frequency of D1853N in total control groups, including normal external control and pedigree internal control, was 18.6% (46/248). The odds ratio was calculated with the logistic regression test, with an estimated relative risk of 2.579 (P = 0.005). The significant difference was observed between the patient-carriers of this alteration and external controls (P = 0.001). The number of controls harboring D1853N polymorphism was higher in internal control compared to external controls, and the difference was statistically significant (P = 0.004). The significant difference was observed between the patient-carriers and external controls and could be considered as a predisposing and diagnostic marker in the population and specifically in the cancer-prone pedigrees.


Breast cancer ATM gene D1853N polymorphism 


  1. 1.
    Mousavi SM, Gouya MM, Ramazani R, Davanlou M, Hajsadeghi N, et al. Cancer incidence and mortality in Iran. Ann Oncol. 2009;20(3):556–63.PubMedCrossRefGoogle Scholar
  2. 2.
    Negrini M, Rasio D, Hampton GM, Sabbioni S, Rattan S, et al. Definition and refinement of chromosome 11 regions of loss of heterozygosity in breast cancer: identification of a new region at 11q23.3. Cancer Res. 1995;55(14):3003–7.PubMedGoogle Scholar
  3. 3.
    Laake K, Launonen V, Niederacher D, Gudlaugsdottir S, Seitz S, et al. Loss of heterozygosity at 11q23.1 and survival in breast cancer: results of a large European study. Breast Cancer Somatic Genetics Consortium. Genes Chromosom Cancer. 1999;25(3):212–21.PubMedCrossRefGoogle Scholar
  4. 4.
    Hampton GM, Mannermaa A, Winqvist R, Alavaikko M, Blanco G, et al. Loss of heterozygosity in sporadic human breast carcinoma: a common region between 11q22 and 11q23.3. Cancer Res. 1994;54(17):4586–9.PubMedGoogle Scholar
  5. 5.
    Carter SL, Negrini M, Baffa R, Gillum DR, Rosenberg AL, et al. Loss of heterozygosity at 11q22–q23 in breast cancer. Cancer Res. 1994;54(23):6270–4.PubMedGoogle Scholar
  6. 6.
    Sandoval N, Platzer M, Rosenthal A, Dork T, Bendix R, Skawran B, Stuhrmann M, Wegner RD, Sperling K, Banin S, Shiloh Y, Baumer A, Bernthaler U, Sennefelder H, Brohm M, Weber BH, Schindler D. Characterization of ATM gene mutations in 66 ataxia telangiectasia families. Hum Mol Genet. 1999;8(1):69–79.PubMedCrossRefGoogle Scholar
  7. 7.
    Stilgenbauer S, Schaffner C, Litterst A, Liebisch P, Gilad S, et al. Biallelic mutations in the ATM gene in T-prolymphocytic leukemia. Nat Med. 1997;3(10):1155–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Vorechovsky I, Luo L, Dyer MJ, Catovsky D, Amlot PL, et al. Clustering of missense mutations in the ataxia-telangiectasia gene in a sporadic T-cell leukaemia. Nat Genet. 1997;17(1):96–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Stoppa-Lyonnet D, Soulier J, Lauge A, Dastot H, Garand R, et al. Inactivation of the ATM gene in T-cell prolymphocytic leukemias. Blood. 1998;91(10):3920–6.PubMedGoogle Scholar
  10. 10.
    Yuille MA, Coignet LJ, Abraham SM, Yaqub F, Luo L, et al. ATM is usually rearranged in T-cell prolymphocytic leukaemia. Oncogene. 1998;16(6):789–96.PubMedCrossRefGoogle Scholar
  11. 11.
    Knudson AG Jr. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA. 1971;68(4):820–3.PubMedCrossRefGoogle Scholar
  12. 12.
    Shiloh Y, Kastan MB. ATM: genome stability, neuronal development, and cancer cross paths. Adv Cancer Res. 2001;83:209–54.PubMedCrossRefGoogle Scholar
  13. 13.
    Concannon P, Gatti RA. Diversity of ATM gene mutations detected in patients with ataxia-telangiectasia. Hum Mutat. 1997;10(2):100–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Athma P, Rappaport R, Swift M. Molecular genotyping shows that ataxia-telangiectasia heterozygotes are predisposed to breast cancer. Cancer Genet Cytogenet. 1996;92(2):130–4.PubMedCrossRefGoogle Scholar
  15. 15.
    Mehdipour P, Habibi L, Mohammadi-Asl J, Kamalian N, Mehr Azin M. Three-hit hypothesis in astrocytoma: tracing the polymorphism D1853N in ATM gene through a pedigree of the proband affected with primary brain tumor. J Cancer Res Clin Oncol. 2008;134(11):1173–80.PubMedCrossRefGoogle Scholar
  16. 16.
    Broeks A, Urbanus JH, Floore AN, Dahler EC, Klijn JG, et al. ATM-heterozygous germline mutations contribute to breast cancer-susceptibility. Am J Hum Genet. 2000;66(2):494–500.PubMedCrossRefGoogle Scholar
  17. 17.
    FitzGerald MG, Bean JM, Hegde SR, Unsal H, MacDonald DJ, et al. Heterozygous ATM mutations do not contribute to early onset of breast cancer. Nat Genet. 1997;15(3):307–10.PubMedCrossRefGoogle Scholar
  18. 18.
    Izatt L, Greenman J, Hodgson S, Ellis D, Watts S, et al. Identification of germline missense mutations and rare allelic variants in the ATM gene in early-onset breast cancer. Genes Chromosom Cancer. 1999;26(4):286–94.PubMedCrossRefGoogle Scholar
  19. 19.
    Easton DF. Cancer risks in A-T heterozygotes. Int J Radiat Biol. 1994;66(6 Suppl):S177–82.PubMedCrossRefGoogle Scholar
  20. 20.
    Kheirollahi M, Mehrazin M, Kamalian N, Mehdipour P. Expression of cyclin D2, P53, Rb and ATM cell cycle genes in brain tumors. Med Oncol. 2010. doi: 10.1007/s12032-009-9412-8.

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Parvin Mehdipour
    • 1
    Email author
  • Marzieh Mahdavi
    • 1
  • Javad Mohammadi-Asl
    • 1
  • Morteza Atri
    • 2
  1. 1.Department of Medical Genetics, School of MedicineTehran University of Medical SciencesTehranIR Iran
  2. 2.Department of Surgery, Cancer Institute, School of MedicineTehran University of Medical SciencesTehranIR Iran

Personalised recommendations