谷胱甘肽 S-转移酶（GSTM1、GSTT1 和 GSTP1）基因多态性及吸烟对慢性髓细胞白血病易感性和治疗反应的影响。
Influence of glutathione S-transferases (GSTM1, GSTT1, and GSTP1) genetic polymorphisms and smoking on susceptibility risk of chronic myeloid leukemia and treatment response.
机构信息
Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Department of Biology, College of Science, Sulaimani University, Sulaymanyah, Iraq.
出版信息
Mol Genet Genomic Med. 2019 Jul;7(7):e00717. doi: 10.1002/mgg3.717. Epub 2019 May 20.
BACKGROUND
Glutathione S-transferases (GSTs) polymorphisms may impact on chronic myeloid leukemia (CML) risk or heterogeneous responses to Imatinib mesylate (IM). The aim of this study was to evaluate the correlation between GSTs polymorphisms and CML risk, treatment response.
METHODS
We genotyped GSTM1, GSTT1 null deletion polymorphisms, and GSTP1 Ile105Val polymorphism by PCR methods and BCR-ABL transcripts were analyzed by qRT-PCR in 104 CML patients and 104 sex- and age-matched healthy individuals.
RESULTS
Individual analysis showed significant association of GSTM1 (p = 0.008; OR = 0.46; 95% CI: 0.26-0.82) and GSTP1 genes (p = 0.04; OR = 1.56; 95% CI: 1.016-2.423) with CML risk. The combined analysis indicated that GSTM1 null/GSTT1 present, GSTM1-null/GSTP1M*(AG/GG) as well as GSTT1 present/ GSTP1M* genotype were associated with CML risk (ORg(-):2.28; 95% CI: 1.29-4.04; ORgg: 2.85; 95% CI: 1.36-5.97; OR(-)g: 1.75; 95% CI: 0.99-3.06, respectively). The proportion of CML cancer attributable to the interaction of smoking and GSTM1 null, GSTT1null, and GSTP1 M* was 42%, 39%, and 13%, respectively. Patients with GSTM1-null and GSTP1 AG/GG genotype had significantly a lower rate of MMR achievement (p = 0.00; p = 0.009 respectively). Event-free survival (EFS) percentage was similar between GSTM1 null and GSTM1 present patients (p = 0.21).
CONCLUSION
Our study suggests the influence of GSTM1 and GSTP1 polymorphisms on CML risk and treatment response. The interaction between GSTs polymorphisms and smoking plays a significant role on CML susceptibility.
背景
谷胱甘肽 S-转移酶（GSTs）多态性可能影响慢性髓性白血病（CML）的风险或伊马替尼甲磺酸盐（IM）的异质性反应。本研究旨在评估 GSTs 多态性与 CML 风险、治疗反应之间的相关性。
方法
我们通过 PCR 方法检测了 104 例 CML 患者和 104 名年龄和性别匹配的健康个体的 GSTM1、GSTT1 缺失基因型和 GSTP1 Ile105Val 多态性，并通过 qRT-PCR 分析了 BCR-ABL 转录本。
结果
个体分析显示，GSTM1（p=0.008；OR=0.46；95%CI：0.26-0.82）和 GSTP1 基因（p=0.04；OR=1.56；95%CI：1.016-2.423）与 CML 风险显著相关。联合分析表明，GSTM1 缺失/GSTT1 存在、GSTM1 缺失/GSTP1M*（AG/GG）以及 GSTT1 存在/GSTP1M基因型与 CML 风险相关（ORg(-)：2.28；95%CI：1.29-4.04；ORgg：2.85；95%CI：1.36-5.97；OR(-)g：1.75；95%CI：0.99-3.06）。吸烟与 GSTM1 缺失、GSTT1 缺失和 GSTP1 M相互作用导致 CML 癌症的比例分别为 42%、39%和 13%。GSTM1 缺失和 GSTP1 AG/GG 基因型的患者获得微小残留病（MRD）缓解的比例明显较低（p=0.00；p=0.009）。无事件生存（EFS）百分比在 GSTM1 缺失和 GSTM1 存在的患者之间相似（p=0.21）。
结论
我们的研究表明，GSTM1 和 GSTP1 多态性对 CML 风险和治疗反应有影响。GSTs 多态性与吸烟的相互作用对 CML 的易感性有重要影响。
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