Role of CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 genes in the susceptibility to acute leukemias

Abstract

Acute leukemias (ALs) are heterogeneous diseases. Functional polymorphisms in the genes encoding detoxification enzymes cause inter-individual differences, which contribute to leukemia susceptibility. The CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 polymorphisms in ALL (n = 156) and AML (n = 94) patients and 140 healthy controls were genotyped by PCR and/or PCR-RFLP using blood or bone marrow samples. No association was observed between the GSTT1 gene deletion and patients (OR = 0.8, 95% CI = 0.4-1.7 for AMLs and OR = 0.9, 95% CI = 0.5-1.6 for ALLs). Patients with ALL and AML had a higher prevalence of the GSTM1 deletions compared to controls but only the difference among adult AML patients (OR = 2.1, 95% Cl = 1.0-4.2) was statistically significant. The CYP2D6*3 variant allele frequency was lower in the overall acute leukemia patients (0.6%) compared to controls (P = 0.03). CYP2D6*1/*3 genotype frequency also showed a protective association in AML patients (OR = 0.09, 95% Cl = 0.01-1.7; P = 0.04). We also found a risk association for CYP2E1*5 in ALL and AML (OR = 3.6, 95% Cl = 1.4-9.4 and OR = 3.9, 95% Cl = 1.4-10.5, respectively). No association was found for the studied CYP2D6*4, CYP1A1 *2A, and GSTT1 "null" variants and the risk of acute leukemia (ALL or AML). This case-control study suggests a contribution of CYP2E1, CYP2D6, and GSTM1 "null" variants to the development of acute leukemias.