Further subgroup analyses by type of disease revealed that GSTM1, GSTP1 and GSTT1 null genotypes were all significantly associated with elevated individual susceptibility to acute lymphoblastic leukemia, GSTM1 and GSTT1 null genotypes were significantly associated with elevated individual susceptibility to acute myeloid leukemia, and GSTT1 null genotype was also significantly associated with elevated individual susceptibility to chronic leukemia.
In addition, there was moderate evidence that children who carry both the CYP1A1*2A variant and the glutathione S-transferase M1 null genotype have an increased risk of acute lymphoid leukemia.
Significantly increased frequencies of GSTM1 null genotype (M0), GSTT1 null genotype (T0) and GST double null genotype (T0M0) were observed in the both ALL and AML cases as compared to controls.
The association of glutathione S-transferase gene mutations (including GSTT1 and GSTM1) with the prognostic factors and relapse in acute lymphoblastic leukemia.
However, in ALL the CYP1A12A TC genotype was associated with increased risk (OR = 2.02; 95% CI = 1.14-3.58; P = 0.01), whereas the GSTM1 null genotype imparted reduced risk (OR = 0.55; 95% CI = 0.31-0.96; P = 0.03).
We found a significant increased risk for ALL with the GSTM1 null genotype (OR: 1.96, 95%CI=1.08-3.57), but no significant risk was found with the GSTP1 (Ile/Val) genotype (OR: 1.32, 95%CI = 0.74-2.37) and the GSTP1 Val/Val genotype (OR: 1.41, 95%CI=0.5-3.96) alone.
Studying the relationship between polymorphisms of these genes and the outcome of our cases revealed the wild genotype of CYP2D6 significantly influenced the outcome of acute leukaemia particularly in AML cases, while GSTM1 null genotype was associated with bad prognosis among the ALL group.
Our results suggest that GSTM1 and GSTT1, but not GSTP1 polymorphisms, appear to be associated with a modest increase in the risk of acute lymphoblastic leukaemia.
However, when the mutant CYP1A1 and CYP2E1 alleles were considered together with the GSTM1 and GSTP1 risk-elevating genotypes, the risk of ALL was increased further (OR = 10.3; 95% CI = 1.0-111.8; P = 0.05), suggesting a combined effect.
However, when the MLH1 genotypes were combined with genotypes previously shown to influence ALL susceptibility, we found that the MLH1 variant Val-219 further increases the risk of GSTM1 null and CYP1A1*2A genotypes [combined odds ratio (OR) = 6.0, P = 0.002] as well as that of CYP2E1*5 (OR = 15.8, P = 0.001).
When combined with other GST genotypes, we found that the combination of GSTP1*B and GSTM1 null genotypes further increased the risk of ALL (OR = 2.1; 95% CI-1.3-3.4).
When NAT2 slow acetylators were considered together with the other risk-elevating genotypes, GSTM1 null and CYP1A1*2A, the risk of ALL increased further, which showed that the combination of these genotypes is more predictive of risk then either of them independently.
In the present study, polymorphism of GSTM1 were detected by polymerase chain reaction (PCR) in 38 patients with acute lymphocytic leukemia and 75 normal subjects.
The NAT2 slow-acetylator, CYP1A1*2A and GSTM1 null genotypes were shown to be significant risk determinants of ALL (OR=1.6, 1.8 and 1.8, respectively), whereas, polymorphisms in CYP2D6 and GSTT1 genes did not seem to play an important role in the aetiology of ALL.
A PCR technique was used to assay for the null genotype for GSTM1 and GSTT1 in 302 children with ALL, 57 of whom also subsequently developed treatment-related acute myeloid leukemia or myelodysplastic syndrome.