title: CYP2B6 gene single nucleotide polymorphisms and leukemia susceptibility.
abstract: CYP2B6 is a highly variable and polymorphic cytochrome P450 enzyme which plays a vital role in the degradation of some endogenous metabolites, xenobiotics, and harmful compounds. The 516G>T single nucleotide polymorphism (SNP) in exon 4 of CYP2B6 gene may change CYP2B6 enzyme activity and the gene expression in the liver. Carcinogens' failure to be degraded by CYP2B6 may cause DNA injury and cancer. Here, we aimed to evaluate the association between genotype or allele of CYP2B6 516G>T SNP and acute leukemia and myelodysplastic syndrome (MDS). We recruited 300 patients including 164 cases of acute myeloid leukemia (AML), 96 cases of acute lymphoblastic leukemia (ALL, including 17 cases of T-ALL and 79 cases of B-ALL), 40 cases of MDS, as well as 348 unrelated umbilical cord blood as the controls. Karyotype analysis and multiplex reverse transcription-polymerase chain reaction (RT-PCR) was performed to determine different recurrent genetic abnormalities in these cases. Genotype of CYP2B6 516G>T SNP was determined by allele-specific primers PCR, and confirmed by gel electrophoresis and sequencing. The GT and GT + TT genotype frequencies of c.516G>T SNP were higher in ALL (37.5% and 42.7%, respectively, P < 0.01), and AML (37.2% and 40.9%, respectively, P < 0.01) than in control (23.9% and 25.9%, respectively). In the subtypes of acute leukemias, the GT + TT genotype frequency was significantly higher in AML with recurrent genetic abnormalities (41.7%, p < 0.05), in AML-NOS (40.6%, p < 0.01), in acute monoblastic and monocytic leukemia (48.3%, p < 0.01), and in T-ALL (70.6%, p < 0.01) as compared with those in the controls. The frequency of CYP2B6 516 T allele was higher in AML (22.3%, p < 0.01) and ALL (24.0%, p < 0.01) compared with cord blood (13.9%). In different types of acute leukemias, CYP2B6 516 T allele frequency was significantly higher in AML with AML1-ETO (19.2%, p < 0.05), AML-NOS (22.7%, p < 0.01), acute monoblastic and monocytic leukemia (25.9%, p < 0.01), and T-ALL (38.2%, p < 0.01). MDS was unrelated to the genotype and allele frequencies of c.516G>T SNP in CYP2B6. T allele of CYP2B6 516G>T SNP may be one of the risk factors predisposing to the pathogenesis of a majority of ALL and AML, but has no relationship with B-ALL and leukemia with or without chromosome abnormalities.
authors.affiliation: Department of Hematology, Peking University First Hospital, Beijing, China.
authors.forename: Zhong-hai
authors.initials: ZH
authors.lastname: Yuan
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hong-xing
authors.initials: HX
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
mesh_terms: D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065702:Cytochrome P-450 CYP2B6; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000201:enzymology / Q000235:genetics*; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics*; D012307:Risk Factors
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating