Abstract B42: Polymorphism of CYP3A5 gene in Indian chronic myeloid leukemia patients

Abstract

Abstract B42 Objective Chronic myeloid leukemia (CML) is a clonal hematopoetic stem cell disorder characterized by the Philadelphia chromosome. Individuals vary in their ability to metabolize carcinogens and hence to detoxify chemicals, leading to different risk in getting cancer. The human CYP3A5 is a major P450 enzyme in the liver and represents 50% of the total hepatic CYP3A content in people expressing CYP3A5. Therefore, it is suggested that the CYP3A5 is an important genetic contributor to inter-individual differences in CYP3A-dependent drug metabolism. Owing to the importance of CYP3A5 genetic polymorphism as risk factor in various cancers, the study was aimed to detect the prevalence of genetic polymorphism of CYP3A5*3 gene in North Indian CML patients and racially matched controls. Further, it will help to determine the association of these allelic variants if any, as risk factor to develop CML. Materials and Methods Human blood was collected from 50 CML patients and 65 healthy individuals which were age and sex matched. DNA isolation was carried out by standard proteinase K and phenol chloroform method. The prevalence of CYP3A5*3 genotype was examined by PCR-RFLP method. PCR products were separated using 2% agarose gel. In the analysis of the CYP3A5*3 polymorphism, a fragment of 155 base pairs (bp) was amplified by PCR, which was followed by restriction digestion by Dde I. The 155 bp product from the CYP3A5*1 allele was digested into 121 and 34 bp fragments, whereas the PCR product of the CYP3A5*3 was cleaved to 97, 34, and 24 bp fragments. Results The frequencies reported in controls were, 7/65 (10.76%) for homozygous CYP3A5*1/*1 , 28/65 (43.07%) for heterozygous CYP3A5*1/*3 and was 30/65 (46.15%) for homozygous CYP3A5*3/*3 respectively. The frequencies reported in cases were 5/50 (10%), 21/50 (42%) and 24/50 (48%) respectively. There was no significant difference between the frequencies of wild (*1/*1), heterozygous (*1/*3) & mutant allele (*3/*3), (control vs cases). However, when these alleles where compared individually within a class, a higher frequency of heterozygous & mutant allele, was reported as compared to the wild type, both in the cases and in controls. The combined frequency of heterozygous & mutant allele vs wild in controls was 89.22% and 10.76% respectively, and that in cases being 90% and 10% respectively. Discussion It is concluded that there is no association of this polymorphism with the risk of Chronic Myeloid Leukemia. However, due to the variable frequencies of xenobiotic metabolizing polymorphic alleles in different populations, further studies with different populations are required in order to investigate the association of polymorphic variability and its possible role in susceptibility to CML. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B42.