ABSTRACT

Background: A combination of risk factors effecting of genetic susceptibility and environmental exposure may explain the multi-step process of carcinogenesis/leukemogenesis of acute myeloid leukemia (AML).

Objectives: The study objective is to evaluate the role of genetic polymorphisms of human cytochrome P450, namely CYP1A1 & CYP2D6 enzymes, involved in the transformation of chemical and cellular metabolism of drugs and carcinogenic agents as risk factors for AML Sudanese patients.

Methods/design: A case control study was conducted between June 2016and June 2018 at the Radiation and Isotope Center Khartoum (RIKA), Sudan. A total of 265 blood specimens (200AML patients and 65 controls) were investigated for allele frequency and genotypes of CYP1A1*2C and CYP2D6*4. The DNA was extracted from all blood specimens, using Qiagen DNA extraction kit. Standard polymerase chain reaction and Restriction fragment length polymorphism analysis (PCR -RFLP) methods were used for genotyping.

Results: Although no significant variations were evident for CYP1A1 AG genotype, the GG genotype showed significant differences. We also found no difference in frequencies of alleles A and G of gene CYP1A1 between patients. While, there is evidence of increased frequency when compared with control G allele. The genotype of the CYP2D6*4 allele revealed no significant differences between IM (heterozygous) and the mutant homozygous (PM) genotype. The PM allele for the CYP 2D6 gene was high in both patients and controls.

Conclusions: Our findings illustrate that the genetic polymorphisms for xenobiotic metabolizing enzymes CYP1A1 heterozygous AG reveal no significant association with AML, where homozygous GG shows a protective effect. CYP2D6 suggests no association with the risk of AML for both heterozygous IM and the mutant homozygous PM.

Key words: Cytochrome P450, CYP1A1, CYP 2D6 & AML