Leukemia is a type of cancer of the blood or bone marrow that is characterized by an abnormal increase of white blood cells. Leukemia is clinically and pathologically subdivided into a variety of large groups. The risk of developing leukemia may be influenced by polymorphisms of xenobiotic metabolizing enzymes. In this work, we conduct a case-control study to assess the impact of polymorphisms in GSTM1, GSTT1 and NAT2 genes on the risk of developing leukemia. Our data have shown that GSTM1*0 and GSTT1*0 were respectively associated with 2.05 and 4.36 increased risk for acute lymphoblastic leukemia (ALL). We have also shown that GSTM1*0 and GSTT1*0 act additively to increase the risk for ALL. Indeed, patients harbouring the “GSTM1*0/GSTT1*0” genotype were at 11.81-fold increased risk for developing ALL (P=2 10^-5). The risk for developing acute myeloid leukemia (AML) increases on patients with “rapid or intermediate NAT2 genotypes”. Finally, the comparison of leukemia subgroups according to GSTM1, GSTT1 and NAT2 genotypes, suggests that leukemogenesis of different leukemia subgroups is very distinct. In conclusion, our findings suggest that leukemogenesis is associated with carcinogen metabolism and consequently related to environmental exposures.