Background/Aims: The molecular etiology of childhood acute lymphoblastic leukemia (ALL) is likely to involve interactions between environmental factors and genetic make up. Understanding these interactions between various predisposing genes for the risk of developing childhood leukemia is of considerable importance. CYP2E1 is a susceptible gene in this respect, especially for its capacity to bioactivate many procarcinogens including benzene and N-nitrosodimethylamine. The CYP2E1 gene possesses several polymorphisms in humans, and among them, CYP2E1*5B and *6 have been shown to be associated with increased risks of several chemical-induced diseases. There are limited and contradictory data on the association between the CYP2E1*5B variant allele and childhood ALL, and none on such associations of CYP2E1*6 and *7B variant alleles. The aim of this study was to investigate the possible association of CYP2E1*5B, *6 and *7B alleles, alone or in combination, with the risk of incidence of childhood ALL in a Turkish population. Methods: The genotypes for both polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism techniques on 207 healthy controls and 168 patients. Results: Neither locus was associated with the occurrence of childhood ALL. On the other hand, when both CYP2E1*5B and *6 alleles were considered together, the risk of childhood ALL increased significantly (2.9-fold; OR = 2.9, 95% CI 1.0-8.5; p <0.05). Moreover, the presence of at least 2 variant alleles of any combination increased the risk significantly 3.9 times, suggesting a combined effect (OR = 3.9, 95% CI 1.4-11.0). Conclusion: Individuals carrying combinations of CYP2E1*5B, *6 and *7B variants together are likely associated with the risk of developing childhood ALL. Copyright (c) 2007 S. Karger AG, Basel.