Glutathione S-transferase polymorphisms in children with myeloid leukemia: a Children's Cancer Group study.
Glutathione S-transferase polymorphisms in children with myeloid leukemia: a Children's Cancer Group study.
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发表时间：
2000-06
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通讯作者：
S. Davies;Leslie L. Robison;Jonathan D. Buckley;G. Radloff;Julie A. Ross;John P. Perentesis
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作者：
S. Davies;Leslie L. Robison;Jonathan D. Buckley;G. Radloff;Julie A. Ross;John P. Perentesis
GSTM1和GSTT1是多态性基因。酶活性的缺失是由于该基因的纯合遗传缺失，减少了环氧化物和烷化剂等致癌物的解毒，并可能增加癌症风险。我们假设 GST 无效基因型会增加儿童患急性髓系白血病和骨髓增生异常 (AML/MDS) 的风险。从 292 名 AML/MDS 患者的骨髓切片中提取 DNA。 PCR 扩增用于分配病例和对照的 GSTM1 和 GSTT1 基因型。鉴于无效基因型的频率因种族而异，并且大多数病例是白种人，因此分析仅限于 232 例白人（非西班牙裔）病例和 153 例白种人非癌症对照。与对照组相比，AML/MDS 病例中 GSTM1 缺失的频率显着增加 [64% vs 47%；比值比 (OR)，2.0 [95% 置信区间 (CI)，1.3-3.1]； P = 0.001]，而 AML/MDS 病例中 GSTT1 无效基因型的频率与对照组没有统计学差异。 AML 包含生物学上不同的亚型，同质性测试显示仅 GSTM1 的亚型之间存在统计显着差异（P = 0.04；df，8）。特别是，在法国-美国-英国群体 M3 中，GSTM1 无效基因型的频率有所增加 [82%； n = 22； OR，5.1（95% CI，1.6-21.3）] 和 M4 [72%； n = 53； OR，2.9（95% CI，1.4-6.0）]。我们得出的结论是，GSTM1 无效基因型是儿童 AML 的一个重要危险因素，特别是法裔美国人英国群体 M3 和 M4。这可能表明外源性致癌物在儿童 AML 的病因学中发挥着重要作用。
GSTM1 and GSTT1 are polymorphic genes. Absence of enzyme activity is due to homozygous inherited deletion of the gene, reducing detoxification of carcinogens such as epoxides and alkylating agents and potentially increasing cancer risk. We hypothesized that GST null genotype would increase risk of acute myeloid leukemia and myelodysplasia (AML/MDS) in children. DNA was extracted from bone marrow slides of 292 AML/MDS patients. PCR amplification was used to assign GSTM1 and GSTT1 genotypes for cases and controls. Given that the frequency of the null genotype varies by ethnicity and that the majority of the cases were Caucasian, analyses were restricted to 232 white (non-Hispanic) cases and 153 Caucasian non cancer controls. The frequency of GSTM1 null was significantly increased in AML/MDS cases compared with controls [64 versus 47%; odds ratio (OR), 2.0 [95% confidence interval (CI), 1.3-3.1]; P = 0.001], whereas the frequency of GSTT1 null genotype in AML/MDS cases was not statistically different from controls. AML comprises biologically distinct subtypes, and a test for homogeneity revealed a statistically significant difference among subtypes (P = 0.04; df, 8) for GSTM1 only. In particular, there was an increased frequency of GSTM1 null genotypes in French-American-British groups M3 [82%; n = 22; OR, 5.1 (95% CI, 1.6-21.3)] and M4 [72%; n = 53; OR, 2.9 (95% CI, 1.4-6.0)]. We conclude that the GSTM1 null genotype is a significant risk factor for childhood AML, particularly French-American-British groups M3 and M4. This may indicate an important role for exogenous carcinogens in the etiology of childhood AML.