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Biomark Insights. 2009 Dec 22;4:201-9. doi: 10.4137/bmi.s3774.

Enhanced Expression of Radiation-induced Leukocyte CDKN1A mRNA in Multiple Primary Breast Cancer Patients: Potential New Marker of Cancer Susceptibility.

Biomarker insights

Masato Mitsuhashi, David Peel, Argyrios Ziogas, Hoda Anton-Culver

Affiliations

  1. Hitachi Chemical Research Center, Inc., Irvine, CA, USA.

PMID: 20072670 PMCID: PMC2805425 DOI: 10.4137/bmi.s3774

Abstract

This study was designed to discover blood biomarkers of cancer susceptibility using invasive multiple (n = 21), single primary breast cancer (n = 21), and control subjects (n = 20). Heparinized whole blood was incubated at 37 degrees C for 2 hours after 0-10 Gy of radiation, then cell cycle arrest marker CDKN1A and apoptosis marker BBC3 mRNA were quantified. This epidemiological study was practically feasible because radiation-induced mRNA was preserved for at least 1 day whenever blood was stored at 4 degrees C (r(2) = 0.901). Moreover, blood could be stored frozen after radiation treatment (r(2) = 0.797). Radiation-induced CDKN1A and BBC3 mRNA were dose dependent, and the degree of induction of CDKN1A was correlated with that of BBC3 (r(2) = 0.679). Interestingly, multiple primary cases showed higher induction of CDKN1A mRNA than single primary and control groups, whereas BBC3 did not show such differences. The results suggested that cancer susceptibility represented by the multiple primary breast cancer cases was related to over-reaction of CDKN1A mRNA, not BBC3. The study also suggests that ex vivo gene expression analysis could potentially be used as a new tool in epidemiological studies for cancer and radiation sensitivity research.

Keywords: BBC3; CDKN1A; DNA damage; cancer susceptibility Mitsuhashi et al; multiple primary cancer

References

  1. Int J Radiat Biol. 2009 May;85(5):403-12 - PubMed
  2. Mol Cell. 2001 Mar;7(3):673-82 - PubMed
  3. Biotechniques. 1998 Jun;24(6):954-8, 960, 962 - PubMed
  4. Proc Natl Acad Sci U S A. 2004 May 11;101(19):7386-91 - PubMed
  5. Br J Cancer. 2008 Jun 3;98(11):1845-51 - PubMed
  6. Oncogene. 2007 Feb 26;26(9):1317-23 - PubMed
  7. Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11318-23 - PubMed
  8. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7276-80 - PubMed
  9. Int J Radiat Biol. 2008 May;84(5):375-87 - PubMed
  10. Int J Radiat Oncol Biol Phys. 2008 Jul 15;71(4):1236-1244 - PubMed
  11. Cell. 1992 Nov 13;71(4):587-97 - PubMed
  12. Invest New Drugs. 2009 Dec;27(6):579-82 - PubMed
  13. Radiat Res. 2000 Sep;154(3):342-6 - PubMed
  14. Hum Mutat. 1999;14(1):1-8 - PubMed
  15. Nature. 1976 Apr 1;260(5550):444-7 - PubMed
  16. Mutat Res. 2010 Jan 5;683(1-2):91-7 - PubMed
  17. Clin Chem. 2006 Apr;52(4):634-42 - PubMed
  18. Pharm Res. 2008 May;25(5):1116-24 - PubMed
  19. Clin Chem. 2008 Apr;54(4):673-81 - PubMed
  20. Mol Cell. 2001 Mar;7(3):683-94 - PubMed
  21. Science. 2003 Nov 7;302(5647):1036-8 - PubMed

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