Author/Authors :
Lakkireddy، Samyuktha نويسنده Centre for Biotechnology and Bioinformatics, School of Life Sciences, Jawaharlal Nehru Institute of Advanced Studies (JNIAS), Secunderabad, Telangana, India444 , , Aula، Sangeetha نويسنده Centre for Biotechnology and Bioinformatics, School of Life Sciences, Jawaharlal Nehru Institute of Advanced Studies (JNIAS), Secunderabad, Telangana, India , , AVN، Swamy نويسنده Department of Chemical Engineering, Jawaharlal Nehru Technological University Anantapur (JNTUA), Ananthapuramu, Andhra Pradesh, India , , Kapley، Atya نويسنده Centre for Biotechnology and Bioinformatics, School of Life Sciences, Jawaharlal Nehru Institute of Advanced Studies (JNIAS), Secunderabad, Telangana, India , , Rao Digumarti، Raghunadha نويسنده Department of Medical Oncology, Nizam’s Institute of Medical Sciences (NIMS), Punjagutta, Hyderabad, Telangana, India , , Jamil، Kaiser نويسنده ,
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 between
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. Genomic
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 protective
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.
