Polymorphisms of CYP1A1 and glutathione S-transferase and susceptibility to adult acute myeloid leukemia

Abstract

BACKGROUND AND OBJECTIVES: The origin of acute myeloid leukemia (AML) may be explained by a combination of genetic susceptibility factors and environmental exposure. We studied the polymorphisms of cytochrome P450 CYP1A1 and glutathione S-transferase (GST), enzymes involved in the metabolism of carcinogens and anti-cancer drugs, as risk factors for adult AML. DESIGN AND METHODS: The prevalence of CYP1A1*2A, *2B and *4 alleles and of GSTM1 and GSTT1 homozygous deletions was examined in 193 patients with AML and 273 normal individuals using polymerase chain reaction (PCR)-based methods. RESULTS: A higher prevalence of the CYP1A1*4 allele was found in AML patients than in controls (19.1% vs 9.9%, OR =2.2, 95% C.I. 1.3-3.7, p=0.006). GSTT1 homozygous deletions were also more frequent in AML patients (29% vs 19%, OR = 1.7, 95% CI 1.1-2.7, p=0.02). The combination of GSTT1 null genotype and CYP1A1 *2B and *4 alleles further increased the risk of AML (OR =10.2, 95% CI 1.2-83.9, p=0.01, and OR =7.0, 95% CI 2.0-24.8, p=0.001, respectively). INTERPRETATION AND CONCLUSIONS:Polymorphic variants in xenobiotic-metabolism genes, including CYP1A1 and GSTT1, may increase the risk of adult AML, particularly when present together.