| Leukemia is a common childhood cancer that constituting about 33% of all childhood cancers. Acute lymphoblastic leukemia (ALL) constitutes 75% of childhood leukemia and acute myeloblastic leukemia (AML) constitutes 20% of childhood leukemia. Some investigators suggest that childhood leukemia may be linked to inherited genetic susceptibility and environmental factors. The null genotypes for some inherited metabolic enzymes that cause less activity to the mutagenic substances may be one of the bases of childhood leukemia susceptibility.As the phase II metabolizing enzymes, the glutathione S-transferase superfamily (GSTs) enzymes have numerous functions. GSTs can catalyze the conjugation of the electrophilic binding sites of the mutagenic substances with reduced glutathione, and thereby plays a significant role in the inactivation and, occasionally, the activation of some xenobiotics. In addition, GSTs can catalyze the peroxides and hydroperoxides with reduced GSH via glutathione peroxidase and hydroperoxidase activities, then protect the cells from oxygenation. Until present, human's GSTs have been classified at least 8 groups, such as alpha(α), mu(μ), theta(θ), kappa(κ), pi(π), sigma(σ), zeta(ζ) and omega(Ω). GSTM1(μ ), GSTT1(θ) exhibit genetic polymorphisms in population distribution. Now, much attention are paid to the relationship between GSTM1 , GSTT1 genetic polymophisms and etiology of the malignancies. It has been reported that GSTM1, GSTT1 genetic polymorphisms are associated with several malignancies. But the relationship between the GSTM1, GSTT1 geneticpolymorphisms and childhood leukemia remains unknown in China.In addition, GSTs may contribute to anticancer drug resistance. The metabolic substances of GSTs are numerous including some anticancer drugs. The patients with the null genotypes may reduce the metabolic activity and decrease the concentrations of the anticancer drugs in the cells. So, GSTs genetic polymorphisms may influence the outcomes of the childhood leukemia. But there are no related reports in our country.In the present study, the genomic DNA of healthy controls and children with acute leukemia are analyzed, through multiplex polymerase chain reaction (multi-PCR) to determine whether GSTM1 , GSTT1 null genotypes could affect the etiology and outcome of childhood leukemia. It will contribute to the selection of high-risk population and the prediction of treatment outcome.Meterials and methods:1 . Categorizations and clinical data collection:(1) the healthy control group: One hundred and forty six healthy blood donors are selected at random as the controls;(2) ALL group: sixty seven cases. Forty two patients of this group received standard chemotherapy after diagnosis;(3) AML group: thirty two cases.2. Methods:(1) Using proteinase K and ethanol, the genomic DNA were extracted from the perpheral whole blood;(2) The purities and concentrations of the genomic DNA were assayed by spectrophotometer;(3) The genomic DNA were amplified by multi-PCR;(4) The amplified products were visuslized by electrophoresis in 2% agarose gels containing ethidium bromide at 80V for 60 min to determine the genotypes.3. Statistical analysis:The chi-square test and Fisher exact test are used to determine the differences indistribution of the GSTM1 ,GSTT1 null genotypes between the cases and the controls. The chi-square test, Fisher exact test and Pilixon rank-sum test are used to determine the association between the GSTM1 ,GSTT1 null genotype and some high-risk factors for the childhood leukemia. For example, sex, age and white blood cell (WBC) count at diagnosis , French- American-British (FAB) subgroups. The significant level is the rate of less than 0.05. When the null genotype is considered as exposed factor, Odds Ratio (OR) and 95% confidence interval (CI) are also calculated.Results:1. The frequencies of the GSTM1, GSTT1 and GST M1-T1 null genotypes are 52.74%, 49.32% and 24.66% in the healthy controls, respectively;... |
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