The Impact of Genetic Polymorphisms of Cytochrome P450 (CYP1A1&2D6) Gene in the Incidence of Acute Myeloid Leukaemia

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.