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Lakkireddy S, Aula S, Avn S, et al. Association of The Common CYP1A1*2C Variant (Ile462Val Polymorphism) with Chronic Myeloid Leukemia (CML) in Patients Undergoing Imatinib Therapy. Cell J. 2015;17(3):510-9doi: 10.22074/cellj.2015.11.
Lakkireddy, S., Aula, S., Avn, S., Kapley, A., Rao Digumarti, R., & Jamil, K. (2015). Association of The Common CYP1A1*2C Variant (Ile462Val Polymorphism) with Chronic Myeloid Leukemia (CML) in Patients Undergoing Imatinib Therapy. Cell journal, 17(3), 510-9. https://doi.org/10.22074/cellj.2015.11
Lakkireddy, Samyuktha, et al. "Association of The Common CYP1A1*2C Variant (Ile462Val Polymorphism) with Chronic Myeloid Leukemia (CML) in Patients Undergoing Imatinib Therapy." Cell journal vol. 17,3 (2015): 510-9. doi: https://doi.org/10.22074/cellj.2015.11
Lakkireddy S, Aula S, Avn S, Kapley A, Rao Digumarti R, Jamil K. Association of The Common CYP1A1*2C Variant (Ile462Val Polymorphism) with Chronic Myeloid Leukemia (CML) in Patients Undergoing Imatinib Therapy. Cell J. 2015;17(3):510-9. doi: 10.22074/cellj.2015.11. Epub 2015 Oct 07. PMID: 26464823; PMCID: PMC4601872.
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Cell J. 2015;17(3):510-9. doi: 10.22074/cellj.2015.11. Epub 2015 Oct 07.

Association of The Common CYP1A1*2C Variant (Ile462Val Polymorphism) with Chronic Myeloid Leukemia (CML) in Patients Undergoing Imatinib Therapy.

Cell journal

Samyuktha Lakkireddy, Sangeetha Aula, Swamy Avn, Atya Kapley, Raghunadha Rao Digumarti, Kaiser Jamil

Affiliations

  1. Centre for Biotechnology and Bioinformatics, School of Life Sciences, Jawaharlal Nehru Institute of Advanced Studies (JNIAS), Secunderabad, Telangana, India ; Department of Biotechnology, Jawaharlal Nehru Technological Univesrity Anantapur (JNTUA), Ananthapuramu, Andhra Pradesh, India.
  2. Department of Chemical Engineering, Jawaharlal Nehru Technological University Anantapur (JNTUA), Ananthapuramu, Andhra Pradesh, India.
  3. Centre for Biotechnology and Bioinformatics, School of Life Sciences, Jawaharlal Nehru Institute of Advanced Studies (JNIAS), Secunderabad, Telangana, India ; Environmental Genomics Division, Council of Scientific and Industrial Research-National Environmental Engineering Research Institute (CSIR-NEERI), Nagpur, Maharashtra, India.
  4. Department of Medical Oncology, Nizam's Institute of Medical Sciences (NIMS), Punjagutta, Hyderabad, Telangana, India.
  5. Centre for Biotechnology and Bioinformatics, School of Life Sciences, Jawaharlal Nehru Institute of Advanced Studies (JNIAS), Secunderabad, Telangana, India.

PMID: 26464823 PMCID: PMC4601872 DOI: 10.22074/cellj.2015.11

Abstract

OBJECTIVE: Cytochrome P450 is one of the major drug metabolizing enzyme families and its role in metabolism of cancer drugs cannot be less emphasized. The association be- tween single nucleotide polymorphisms (SNPs) in CYP1A1 and pathogenesis of chronic myeloid leukemia (CML) has been investigated in several studies, but the results observed vary based on varied risk factors. The objective of this study was to investigate the risk factors associated with the CYP1A1*2C [rs1048943: A>G] polymorphism in CML patients and its role in therapeutic response to imatinib mesylate (IM) affecting clinico-pathological parameters, in the Indian population.

MATERIALS AND METHODS: In this case-control study, CYP1A1*2C was analysed in CML patients. After obtaining approval from the Ethics Committee of oncology hospital, we collected blood samples from 132 CML patients and 140 matched controls. Genom- ic DNA was extracted and all the samples were analysed for the presence of the CYP1A1*2C polymorphism using allele-specific polymerase chain reaction, and we examined the relationship of genotypes with risk factors such as gender, age, phase of the disease and other clinical parameters.

RESULTS: We observed a significant difference in the frequency distribution of CYP1A1*2C genotypes AA (38 vs. 16%, P=0.0001), AG (57 vs. 78%, P=0.0002) and GG (5 vs. 6%, P=0.6635) between patients and controls. In terms of response to IM therapy, significant variation was observed in the frequencies of AA vs AG in major (33 vs 67%) and poor (62 vs 31%) hematological responders, and AA vs AG in major (34 vs. 65%) and poor (78 vs. 22%) cytogenetic responders. However, the patients with the GG homozygous genotype did not show any significant therapeutic outcome.

CONCLUSION: The higher frequency of AG in controls indicates that AG may play a protec- tive role against developing CML. We also found that patients with the AG genotype showed favorable treatment response towards imatinib therapy, indicating that this polymorphism could serve as a good therapeutic marker in predicting response to such therapy.

Keywords: CYP1A1; Chronic Myeloid Leukemia; Cytochrome P-450 Enzyme System; Imatinib; Polymorphism

References

  1. Blood Cells Mol Dis. 2004 Nov-Dec;33(3):326-9 - PubMed
  2. Clin Cancer Res. 2006 Dec 15;12(24):7374-9 - PubMed
  3. Int Arch Occup Environ Health. 2000 Mar;73(2):71-85 - PubMed
  4. JAMA. 2001 Aug 22-29;286(8):895-8 - PubMed
  5. Blood. 2000 Nov 15;96(10):3343-56 - PubMed
  6. J Clin Oncol. 2009 Dec 10;27(35):6041-51 - PubMed
  7. Front Biosci. 2004 May 01;9:1967-76 - PubMed
  8. Cancer Biomark. 2009;5(1):33-40 - PubMed
  9. Cancer Chemother Pharmacol. 2013 Sep;72(3):529-35 - PubMed
  10. Hematol Oncol Clin North Am. 2004 Jun;18(3):641-56, ix - PubMed
  11. Hematology Am Soc Hematol Educ Program. 2008;:419-26 - PubMed
  12. Nat Rev Cancer. 2007 Jun;7(6):441-53 - PubMed
  13. Cancer Epidemiol. 2010 Oct;34(5):587-92 - PubMed
  14. Leuk Lymphoma. 2007 Jun;48(6):1211-5 - PubMed
  15. Blood. 2004 Jun 1;103(11):4010-22 - PubMed
  16. Pharmacol Rev. 2004 Mar;56(1):53-102 - PubMed
  17. Leuk Lymphoma. 2007 Jun;48(6):1070-1 - PubMed
  18. Am J Hematol. 2003 Jul;73(3):154-60 - PubMed
  19. Nucleic Acids Res. 1991 Oct 11;19(19):5444 - PubMed
  20. Swiss Med Wkly. 2008 Jan 12;138(1-2):12-7 - PubMed
  21. J Clin Oncol. 2008 Oct 10;26(29):4806-13 - PubMed
  22. Pediatr Blood Cancer. 2004 Oct;43(5):560-7 - PubMed
  23. Cancer Invest. 2009 Oct;27(8):869-76 - PubMed
  24. Blood. 2007 May 15;109(10):4143-50 - PubMed
  25. Carcinogenesis. 2002 Mar;23(3):379-80 - PubMed
  26. N Engl J Med. 2006 Dec 7;355(23):2408-17 - PubMed
  27. Environ Mol Mutagen. 2004;43(2):100-9 - PubMed
  28. Biopharm Drug Dispos. 2008 Mar;29(2):103-18 - PubMed

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