The potential effect of gender in combination with common genetic polymorphisms of drug-metabolizing enzymes on the risk of developing acute leukemia

From the Laboratory of Molecular Biology, Department of Medical Biopathology, Hospital Universitario La Fe, Valencia, Spain (PB, MC, EB); Cytogenetics, Service of Hematology, Hospital Universitario La Fe, Valencia, Spain (JC); Department of Genetics, University of Navarra, Pamplona, Spain (M-JC); Hematology, Hospital Clínic de Barcelona, Barcelona, Spain (DC); Service of Hematology, Hospital Reina Sofia, Córdoba, Spain (JR-G); Clinical Hematology, Service of Hematology, Hospital Universitario La Fe, Valencia, Spain (MAS) Correspondence: Pascual Bolufer Gilabert, Laboratorio de Biología Molecular, Escuela de Enfermería 7ª. Hospital Universitario la Fe, Avda. Campanar 21, 46009 Valencia, Spain. E-mail: bolufer_pas{at}gva.es Background and Objectives: We examined common polymorphisms in the genes for glutathione S-transferase ( GST ), cytochrome P450 ( CYP ), quinone oxoreductase ( NQO1 ), methylene tetrahydrofolate reductase ( MTHFR ), and thymidylate synthetase ( TYMS ) and the role of gender associated with the susceptibility to de novo acute leukemia (AL). Design and Methods: We conducted a case-control study analyzing the prevalence of the polymorphisms CYP1A1*2A , CYP2E1*5B, CYP3A4*1B , del{GSTT1}, del{GSTM1}, NQO1*2 , MTHFR C6777 , and TYMS 2R/3R in 443 patients with AL [302 with acute myeloblastic leukemia (AML) and 141 with acute lymphoblastic leukemia (ALL)] and 454 control volunteers, using polymerase chain reaction (PCR)-based methods. Results: We found a higher incidence of del{GSTT1} in patients with AML than among controls (25.6% vs. 13.7%, OR=2.2, p