title: Association of The Common CYP1A1*2C Variant (Ile462Val Polymorphism) with Chronic Myeloid Leukemia (CML) in Patients Undergoing Imatinib Therapy.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Samyuktha
authors.initials: S
authors.lastname: Lakkireddy
authors.affiliation: 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.
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Aula
authors.affiliation: Department of Chemical Engineering, Jawaharlal Nehru Technological University Anantapur (JNTUA), Ananthapuramu, Andhra Pradesh, India.
authors.forename: Swamy
authors.initials: S
authors.lastname: Avn
authors.affiliation: 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.
authors.forename: Atya
authors.initials: A
authors.lastname: Kapley
authors.affiliation: Department of Medical Oncology, Nizam's Institute of Medical Sciences (NIMS), Punjagutta, Hyderabad, Telangana, India.
authors.forename: Raghunadha
authors.initials: R
authors.lastname: Rao Digumarti
authors.affiliation: Centre for Biotechnology and Bioinformatics, School of Life Sciences, Jawaharlal Nehru Institute of Advanced Studies (JNIAS), Secunderabad, Telangana, India.
authors.forename: Kaiser
authors.initials: K
authors.lastname: Jamil
keywords: CYP1A1; Chronic Myeloid Leukemia; Cytochrome P-450 Enzyme System; Imatinib; Polymorphism