CYP2C19 Polymorphism in Childhood Hematological Malignancy

Abstract

Cytochrome P450 2C19 (CYP2C19) participates in the metabolism of many clinically important drugs and many xenobiotic compounds. Genetic polymorphisms of the CYP2C19 gene are described to have possible effect on drug treatment and increasing susceptibility to carcinogenic substances. The aim of this study was to determine the frequencies of the major polymorphic CYP2C19 alleles (CYP2C19*2 and CYP2C19*3) and to investigate their association with occurrence of childhood hematological malignancies and/or age of onset of the disease in the investigated patients with comparison to normal subjects. The polymorphism of CYP2C19 was analyzed by a genotyping technique, based on polymerase chain reaction (PCR) followed by restriction enzyme analysis. EDTA blood samples were obtained from 52 previously diagnosed hematological malignancy children (45 from El-Nasser hospital and 7 from the European Gaza hospital) and from 52 normal subjects. The DNA was extracted from the EDTA blood sample for each child. The frequencies of each allele in the cancer group and the control group were compared. In the patient group the frequencies of CYP2C19*2 and CYP2C19*3 were 9.62% and 0.96%, respectively, while in the control group the respective frequencies were 5.77% and 2.88%. These percentages show that there is no significant difference between the control group and the patient group in terms of the frequencies of CYP2C19*2 and CYP2C19*3. The genotyping analysis showed the following results: 15.39% (1*/2*), 1.92% (1*/3*), 1.92% (2*/2*), and 80.77% (1*/1*) in the patients while in the normal subjects the results were 7.69% (1*/2*) , 5.77% (1*/3*), 1.92% (2*/2*), and 84.61% (1*/1*). Data also showed that there is no significant Correlation between the onset age and the polymorphism of the CYP2C19. Moreover, the frequency of affected males was more than that of females. In conclusion, no significant association was found between the CYP2C19 polymorphism and the occurrence or the onset age of the childhood hematological malignancies. Further studies are needed to investigate more CYP2C19 alleles and other important CYP genes polymorphisms in cancer patients.