Skip to main content
SpringerLink
Log in

Determination of variations of the primary structure of the UGT1A1, DPYD, GSTP1, and ABCB1 genes involved in the metabolism of antitumor agents

  • Molecular Biophysics
  • Published:
Biophysics Aims and scope Submit manuscript

Abstract

A individual approach to the treatment of cancer patients, which takes the genetic features of the patient’s metabolism into account, allows one to choose an appropriate drug and its dose, that increases the efficiency of therapy and prevents the development of side toxic effects. For this purpose, we developed a biological microarray-based method for studying the primary structure of patient DNA and identifying polymorphisms in the UGT1A1, DPYD, GSTP1, and ABCB1 genes associated with alterations in xenobiotic metabolism. Genotyping of samples from 89 cancer patients and 15 healthy donors was carried out using the developed microarray. The results of determination of the primary structure of DNA samples coincided completely with the control sequencing. To increase the specificity of determination of polymorphic variants of the UGT1A1 gene, we used hybridization probes containing LNA nucleotides. The frequencies of polymorphic allelic variants of the UGT1A1*28, DPYD*2A, GSTP1 (I105V), and ABCB1 (C3435T) genes in the studied sample were 0.39, 0, 0.33, and 0.57, respectively.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ABCB1:

ATP-binding cassette subfamily B member 1

DPYD:

dihydropyrimidine dehydrogenase

GST:

glutathione S-transferase

LNA:

locked nucleic acid

ТА:

thymine−adenine

UGT:

uridine 5'-diphosphoglucuronosyl transferase

References

  1. C. P. Strassburg, Pharmacogenomics 9, 703 (2008).

    Article  Google Scholar 

  2. P. J. Bosma, J. R. Chowdhury, C. Bakker, et al., N. Engl. J. Med. 333, 1171 (1995).

    Article  Google Scholar 

  3. R. H. Tukey, C. P. Strassburg, and P. I. Mackenzie, Mol. Pharmacol. 62, 446 (2002).

    Article  Google Scholar 

  4. L. E. Carlini, N. J. Meropol, J. Bever, et al., Clin. Cancer. Res. 11, 1226 (2005).

    Google Scholar 

  5. F. Innocenti, S. D. Undevia, L. Iyer, et al., J. Clin. Oncol. 22, 1382 (2004).

    Article  Google Scholar 

  6. E. Marcuello, A. Altes, A. Menoyo, et al., Br. J. Cancer. 91, 678 (2004).

    Google Scholar 

  7. L. K. Mattison, R. Soong, and R. B. Diasio, Pharmacogenomics 3, 485 (2002).

    Article  Google Scholar 

  8. T. Takechi, H. Okabe, K. Ikeda, et al., Oncol. Rep. 14, 33 (2005).

    Google Scholar 

  9. P. M. Hoff, Invest. New Drugs 18, 331 (2000).

    Article  Google Scholar 

  10. B. van Kuilenburg, P. Vreken, N. G. Abeling, et al., Hum. Genet. 104, 1 (1999).

    Article  Google Scholar 

  11. R. Meinsma, P. Fernandez-Salguero, A. B. van Kuilenburg, et al., DNA Cell Biol. 14, 1 (1995).

    Article  Google Scholar 

  12. X. Wei, H. L. McLeod, J. McMurrough, et al., J. Clin. Invest. 98, 610 (1996).

    Article  Google Scholar 

  13. P. Vreken, A. B. van Kuilenburg, R. Meinsma, et al., J. Inherit. Metab. Dis. 19, 645 (1996).

    Article  Google Scholar 

  14. F. Ali-Osman, O. Akande, G. Antoun, et al., J. Biol. Chem. 272, 10004 (1997).

    Article  Google Scholar 

  15. M. A. Watson, R. K. Stewart, G. B. Smith, et al., Carcinogenesis 19, 275 (1998).

    Article  Google Scholar 

  16. J. Stoehlmacher, D. J. Park, W. Zhang, et al., Br. J. Cancer. 91, 344 (2004).

    Google Scholar 

  17. T. Lecomte, B. Landi, P. Beaune, et al., Clin. Cancer Res. 12, 3050 (2006).

    Article  Google Scholar 

  18. A. Ruzzo, F. Graziano, F. Loupakis, et al., J. Clin. Oncol. 25, 1247 (2007).

    Article  Google Scholar 

  19. L. Zhang, T. Sun, B. N. Zhang, et al., Chin. Med. J. (Engl.) 124, 199 (2011).

    Google Scholar 

  20. F. Higgins, Nature 446, 749 (2007).

    Article  ADS  Google Scholar 

  21. G. D. Kruh, Oncogene 22, 7262 (2003).

    Article  Google Scholar 

  22. R. A. Randle, S. Raguz, C. F. Higgins, et al., Biochem. J. 406, 445 (2007).

    Article  Google Scholar 

  23. Y. Rubina, S. V. Pan’kov, E. I. Dementieva, et al., Anal. Biochem. 325, 92 (2004).

    Article  Google Scholar 

  24. R. Heydarov, S. Titov, M. Abramov, et al., Cancer Biomark. doi (2016). doi 10.3233/CBM-160165

    Google Scholar 

  25. E. E. Fesenko, R. N. Heydarov, E. V. Stepanova, et al., Clin. Chem. Lab. Med. 51, 1177 (2013).

    Article  Google Scholar 

  26. C. Skarke, S. Grцsch, G. Geisslinger, et al., Int. J. Clin. Pharmacol. Ther. 42, 133 (2004).

    Article  Google Scholar 

  27. Y. Hasegawa, T. Sarashina, M. Ando, et al., Clin. Chem. 50, 1479 (2004).

    Article  Google Scholar 

  28. J. Watanabe, Y. Mitani, Y. Kawai, et al., Biotechniques 43, 479 (2007).

    Article  Google Scholar 

  29. C. K. Huang, A. Dulau, C. J. Su-Rick, et al., Diagn. Mol. Pathol. 16, 50 (2007).

    Article  Google Scholar 

  30. D. Pirulli, M. Giordano, D. Puzzer, et al., Clin. Chem. 46, 129 (2000).

    Google Scholar 

  31. J. R. Harraway, P. M. George, Clin. Chem. 51, 2183 (2005).

    Article  Google Scholar 

  32. E. Beutler, T. Gelbart, and A. Demina, Proc. Natl. Acad. Sci. U. S. A. 95, 8170 (1998).

    Article  ADS  Google Scholar 

  33. D. Hall, G. Ybazeta, G. Destro-Bisol, et al., Pharmacogenetics 9, 591 (1999).

    Article  Google Scholar 

  34. M. Raida, W. Schwabe, P. Häusler, et al., Clin. Cancer Res. 7, 2832 (2001).

    Google Scholar 

  35. H. S. Süzen, N. Yüce, G. Güvenç, et al., Eur. J. Clin. Pharmacol. 61, 881 (2005).

    Article  Google Scholar 

  36. S. A. Ridge, J. Sludden, O. Brown, et al., Br. J. Clin. Pharmacol. 46, 151 (1998).

    Article  Google Scholar 

  37. B. van Kuilenburg, E. W. Muller, J. Haasjes, et al., Clin. Cancer Res. 7, 1149 (2001).

    Google Scholar 

  38. T. Ceric, N. Obralic, L. Kapur-Pojskic, et al., Basic Med. Sci. 10, 133 (2010).

    Google Scholar 

  39. A. Ofverholm, E. Arkblad, S. Skrtic, et al., Clin. Biochem. 43, 331 (2010).

    Article  Google Scholar 

  40. A. Uzunkoy, F. Dilmec, A. Ozgonul, et al., Anticancer Res. 27, 3899 (2007).

    Google Scholar 

  41. J. Ciccolini, C. Mercier, A. Evrard, et al., Ther. Drug Monit. 28, 678 (2006).

    Article  Google Scholar 

  42. S. M. Offer, A. M. Lee, L. K. Mattison, et al., Clin. Pharmacol. Ther. 94, 158 (2013).

    Article  Google Scholar 

  43. P. Georgiadis, N. A. Demopoulos, J. Topinka, et al., Toxicol. Lett. 149, 269 (2004).

    Article  Google Scholar 

  44. A. Gsur, G. Haidinger, S. Hinteregger, et al., Int. J. Cancer. 95, 152 (2001).

    Article  Google Scholar 

  45. T. Ishii, T. Matsuse, S. Teramoto, et al., Thorax 54, 693 (1999).

    Article  Google Scholar 

  46. C. Dandara, J. Sayi, C. M. Masimirembwa, et al., Clin. Chem. Lab. Med. 40, 952 (2002).

    Article  Google Scholar 

  47. C. P. Wild, F. Yin, P. C. Turner, et al., Int. J. Cancer 86, 1 (2000).

    Article  Google Scholar 

  48. T. Sakaeda, T. Nakamura, and K. Okumura, Pharmacogenomics 4, 397 (2003).

    Article  Google Scholar 

  49. M. Schwab, M. Eichelbaum, and M. F. Fromm, Annu. Rev. Pharmacol. Toxicol. 43, 285 (2003).

    Article  Google Scholar 

  50. S. Dey, Expert. Opin. Drug Deliv. 3, 23 (2006).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia

    S. V. Titov, R. N. Heydarov, M. E. Abramov, E. N. Timofeev & V. M. Mikhailovich

Authors
  1. S. V. Titov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. N. Heydarov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. E. Abramov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. N. Timofeev
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. V. M. Mikhailovich
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. M. Mikhailovich.

Additional information

Original Russian Text © S.V. Titov, R.N. Heydarov, M.E. Abramov, E.N. Timofeev, V.M. Mikhailovich, 2017, published in Biofizika, 2017, Vol. 62, No. 2, pp. 276–283.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Titov, S.V., Heydarov, R.N., Abramov, M.E. et al. Determination of variations of the primary structure of the UGT1A1, DPYD, GSTP1, and ABCB1 genes involved in the metabolism of antitumor agents. BIOPHYSICS 62, 207–213 (2017). https://doi.org/10.1134/S0006350917020270

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006350917020270

Keywords

Search

Navigation