Impact of cyp3a5 and cyp3a4 genetic polymorphisms on susceptibility risk of chronic myeloid leukemia and treatment response

Parisa Pazooki,1,* Golale rostami ,2 Mohammad hamid ,3 Hasan jalaeikhoo ,4

1. Department of biological sciences, ،Tehran north branch, Islamic Azad university, Tehran, Iran
2. Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
3. Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
4. AJA Cancer Research Center (ACRC), AJA University of Medical Science, Tehran, Iran

Abstract

Introduction

Cyp3a5 and cyp3a4 are the members of the cyp3a gene family which metabolizes 50% of therapeutic drugs and steroid hormones. these polymorphisms exhibit inter-individual differences in drug metabolism and increased risk of cancer.this study aimed to investigate influence of polymorphisms of cyp3a5*6 ,cyp3a5*3 and cyp3a4*1b on susceptibility to chronic myeloid leukemia (cml) in patients on imatinib treatment and to determine whether polymorphisms of these two genes could predict the response to imatinib in iranian cml patients for the first time.

Methods

the genotype distribution and allele frequencies of three cyp3a4*1b, cyp3a5*6 and cyp3a5*3 polymorphisms were determined in 100 cml patients and 100 controls by using of pcr-rflp. all patients received imatinib and were followed for at least three years. the response to imatinib was evaluated by recording the cytogenetic response according to the european leukemia net criteria.

Results

The cyp3a5*3/*6 mutant allele and genotype frequency were higher in patients compared to controls (p< 0.05). there was an association between cyp3a5*3 and cyp3a5*6 polymorphisms, smoking status and susceptibility to cml development (p=0.001). no association between these polymorphisms and cytogenetic response to imatinib therapy was detected (p>0.05)). no significant difference in genotype frequency was found between wild and mutant genotypes in patients when sex and smoking status were considered.

Conclusion

Our study suggests that the cyp3a5 polymorphisms are significantly associated with the risk of cml development .

Keywords

Cml, polymorphism, cyp3a5, cyp3a4, iranian population