Department of Medical Biology, School of Medicine, Ankara University, Ankara, Turkey.
Hematol Oncol. 2012 Sep;30(3):150-5. doi: 10.1002/hon.1018. Epub 2011 Oct 4.
Glutathione S-transferases (GSTs) are phase II enzymes that detoxify hazardous xenobiotics including carcinogens. Inter-individual variations in GSTM1 and GSTT1 loci have been associated with several types of cancer, including leukemias. In this study, we investigated the possible association between GSTM1 and GSTT1 polymorphisms and susceptibility to chronic myeloid leukemia (CML) in a Turkish population. In a case-control study, 106 CML patients and 190 healthy controls were evaluated for GSTM1 and GSTT1 polymorphisms. GSTM1 null (GSTM1(-)) genotype frequencies in CML cases and controls were 45.3% and 42.6%, respectively. GSTT1 null (GSTT1(-)) genotype frequencies were 44.3% and 18.4%, respectively. The frequency of the GSTT1(-) genotype among CML patients was significantly higher than in controls [odds ratio (OR) 3.53, 95% confidence interval (CI) 2.08-6.00; P < 0.0001]. Individuals with the GSTM1(-) genotype did not have increased risk of CML [OR: 1.11; 95% CI: 0.69-1.80; P = 0.714]. The combined GSTM1(-)/GSTT1(-) genotype was significantly associated with risk of CML compared to the GSTM1(+) /GSTT1(+) genotype which was most frequent in both cases and controls [OR: 9.47; 95% CI: 3.61-24.87]. Similar findings have only been obtained in Turkish and Indian populations but not elsewhere. The GSTM1(+) /GSTT1(-) genotype was associated with a 2.5-fold increased risk compared with the GSTM1(-)/GSTT1(+) genotype, the second most frequent genotype (OR; 2.46; 95% CI: 1.17, 5.20), suggesting a complex interaction between GSTM1 and GSTT1. Our results indicate an association between the GSTT1(-) genotype, either alone or in combination with GSTM1(-) genotype, and risk of CML, suggesting a possible interaction between GSTM1 and GSTT1. These findings, which are possibly restricted to Turkey and India, warrant further research.
谷胱甘肽 S-转移酶(GSTs)是一种 II 相酶,可解毒包括致癌物在内的有害异源物质。GSTM1 和 GSTT1 基因座的个体间变异与多种类型的癌症有关,包括白血病。在这项研究中,我们在土耳其人群中研究了 GSTM1 和 GSTT1 多态性与慢性髓性白血病(CML)易感性之间的可能关联。在病例对照研究中,评估了 106 例 CML 患者和 190 名健康对照者的 GSTM1 和 GSTT1 多态性。CML 病例和对照组的 GSTM1 缺失(GSTM1(-))基因型频率分别为 45.3%和 42.6%。GSTT1 缺失(GSTT1(-))基因型频率分别为 44.3%和 18.4%。CML 患者中 GSTT1(-)基因型的频率明显高于对照组[比值比(OR)3.53,95%置信区间(CI)2.08-6.00;P < 0.0001]。具有 GSTM1(-)基因型的个体患 CML 的风险没有增加[OR:1.11;95% CI:0.69-1.80;P = 0.714]。与在病例和对照组中最常见的 GSTM1(+) /GSTT1(+)基因型相比,GSTM1(-)/GSTT1(-)基因型与 CML 的风险显著相关[OR:9.47;95% CI:3.61-24.87]。仅在土耳其和印度人群中获得了类似的发现,但在其他地方没有。与第二常见的基因型 GSTM1(-)/GSTT1(+)相比,GSTM1(+) /GSTT1(-)基因型与 CML 的风险增加 2.5 倍相关[OR;2.46;95% CI:1.17,5.20],表明 GSTM1 和 GSTT1 之间存在复杂的相互作用。我们的结果表明,GSTM1 和 GSTT1 缺失基因型单独或联合与 CML 风险相关,表明 GSTM1 和 GSTT1 之间可能存在相互作用。这些发现可能仅限于土耳其和印度,需要进一步研究。