Abstract
BackgroundIt has been postulated that the interaction between environmental risk factors and genetic susceptibility is a possible cause for the development of acute myeloid leukemia (AML). Cytochrome P450 (CYP) detoxification enzymes are responsible for the elimination of oxidative stress. Genetic polymorphisms in these enzymes may cause AML due to enhanced accumulation of reactive oxygen species. To study the association between CYP3A4 (A290G) and CYP2B6 (G516T) gene polymorphisms and the predisposition and prognosis of AML, 50 upfront AML patients and 50 healthy individuals were genotyped for CYP2B6 (G516T) and CYP3A4 (A290G) single-nucleotide polymorphisms (SNPs) using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) technique. The polymorphisms were evaluated in relation to the response to chemotherapy and survival.ResultsCYP2B6 gene mutation carries a threefold risk of developing AML (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.3–6.9), whereas CYP3A4 gene mutation carries approximately fourfold risk (OR, 3.8; 95% CI, 1.4–10.1). The presence of combined gene mutation conferred about 15-fold increased risk of developing AML compared with the presence of a single gene mutation (OR, 14.8; 95% CI, 1.8–124.2). CYP3A4 gene mutation is associated with worse overall survival (P = 0.030).ConclusionCYP enzyme gene polymorphisms are associated with the development of AML. Elimination of oxidative stress in genetically susceptible individuals may decrease the risk of AML and may improve survival.
Highlights
It has been postulated that the interaction between environmental risk factors and genetic susceptibility is a possible cause for the development of acute myeloid leukemia (AML)
This study aimed to evaluate the association between CYP2B6 (G515T) and CYP3A4 (A290G) Single nucleotide polymorphism (SNP) and AML susceptibility in Egyptian patients and their effect on the response to chemotherapy
The results of this study provide an evidence for the possible pathogenetic role of the CYP2B6 and CYP3A4 polymorphisms on the risk of developing AML
Summary
It has been postulated that the interaction between environmental risk factors and genetic susceptibility is a possible cause for the development of acute myeloid leukemia (AML). Acute myeloid leukemia (AML), which is characterized by the infiltration of the bone marrow (BM), blood, and other tissues by proliferative, clonal, abnormally differentiated and sometimes poorly differentiated cells of hematopoietic origin, is the most common type of acute leukemia in adults [1, 2] The etiology of this disease is almost unknown; the interaction between. Certain single-nucleotide polymorphisms (SNPs) at the CYP genetic loci (CYP2D6, CYP1A1, CYP3A5, and CYP2E1) may be considered as risk factors for many types of cancer and hematological malignancies, such as AML, acute lymphoblastic leukemia, and myelodysplastic syndromes, through the inactivation of enzymatic activity [8,9,10,11,12,13,14]. Individuals carrying the T allele (TT) have a lower enzymatic activity than individuals carrying the wild-type G allele (GG), whereas individuals carrying the genotype GT show intermediate activity [15]
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