1. Department of Molecular Medicine, Biotechnology Research Center Pasteur Institute of Iran 3. Department of Molecular Medicine, Biotechnology Research Center Pasteur Institute of Iran
Xenobiotic- metabolizing enzymes compose an important line of defence against a variety of carcinogenes and environmental chemicals . many of these enzymes are genetically polymorphic and have been associated with wide inter-individual differences in drug metabolism and increased risk of cancer.the aim of this study was to identify the correlation between cyp2d6 and cyp3a4 genetic polymorphisms and cml cancer risk, treatment response and smoking as genetic modifiers in the etiology of cml disease in the iranian population , for the first time.
Allele and genotype frequency distributions of cyp2d6*3,cyp2d6*4 and cyp3a4*18 variants were analysed in a total of 103 cml patients on imatinib treatment and 103 healthy controls using pcr-rflp. clinical information regarding to cytogenetic response of patients was collected from their clinical file.
The cyp2d6*3 and cyp3a4*18 mutant allelic frequencies were not detected in iranian population . however,the cyp2d6*4 mutant allele and genotype frequency was higher in patients compared to controls (p< 0.05), and also was higher in males than to females (p= 0.01).we indicated an association between cyp2d6*4 polymorphism, smoking status and susceptibility to cml development (p<0.05). the achieving of cytogenetic response was lower in patients with mutant allele than to wild types (p= 0.002; or=4.51;95% ci, 1.34-12.35).
These findings suggest that the risk of cml and resistance to imatinib may be associated with cyp2d6*4 polymorphism.
Cml, polymorphism, cyp2d6, cyp3a4, iranian population