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

Objective: cytochrome p450 is one of the major drug metabolizing enzyme families andits role in metabolism of cancer drugs cannot be less emphasized. the association betweensingle nucleotide polymorphisms (snps) in cyp1a1 and pathogenesis of chronicmyeloid leukemia (cml) has been investigated in several studies, but the results observedvary based on varied risk factors. the objective of this study was to investigate the riskfactors associated with the cyp1a1*2c [rs1048943: a > g] polymorphism in cml patientsand its role in therapeutic response to imatinib mesylate (im) affecting clinico-pathologicalparameters, in the indian population.materials and methods: in this case-control study, cyp1a1*2c was analysed in cmlpatients. after obtaining approval from the ethics committee of oncology hospital, wecollected blood samples from 132 cml patients and 140 matched controls. genomicdna was extracted and all the samples were analysed for the presence of thecyp1a1*2c polymorphism using allele-specific polymerase chain reaction, and weexamined the relationship of genotypes with risk factors such as gender, age, phaseof the disease and other clinical parameters.results: we observed a significant difference in the frequency distribution of cyp1a1*2cgenotypes 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, significantvariation was observed in the frequencies of aa vs. ag in major (33 vs. 67%) and poor (62vs. 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 genotypedid not show any significant therapeutic outcome.conclusion: the higher frequency of ag in controls indicates that ag may play a protectiverole against developing cml. we also found that patients with the ag genotype showedfavorable treatment response towards imatinib therapy, indicating that this polymorphismcould serve as a good therapeutic marker in predicting response to such therapy.