Kassogue Yaya, Dehbi Hind, Quachouh Meryem, Quessar Asma, Benchekroun Said, Nadifi Sellama
Genetics and Molecular Pathology Laboratory, Medical School of Casablanca, 19 Rue Tarik Ibnou Ziad, Casablanca, BP 9154 Morocco.
Department of Onco-Hematology, Ibn Rochd University Hospital, Casablanca, Morocco.
Springerplus. 2015 May 1;4:210. doi: 10.1186/s40064-015-0966-y. eCollection 2015.
Chronic myeloid leukemia (CML), as most of cancers results from a complex interaction between genetic or non genetic factors. Exposures to xenobiotics endogenous or exogenous associated with a reduced individual ability in detoxifying activity, constitutes a risk of developing cancer. It is known that polymorphism of glutathione S-transferases (GSTs) genes affects the detoxification of xenobiotics. Thus, we conducted a case-control study in which 92 patients (Mean age ± SD, 40.62 ± 12.7 years) with CML and 93 healthy unrelated controls (Mean age ± SD, 41.38 ± 13.4 years) have participated. GSTM1 and GSTT1 genotypes were determined by multiplex polymerase chain reaction. Logistic regression was used to assess the possible link between GSTM1 and GSTT1 null genotypes and CML as well as between combined genotypes and CML. GSTM1 null genotype frequency was slightly higher in patients than control (48.9% vs. 40.9%) but, it was not associated with CML (OR 95% CI, 1.4, 0.78-2.48; p = 0.271). Moreover, GSTT1 null genotype frequency showed a similar trend between patients and control (17.4% vs. 9.7%; OR 95% CI, 1.97, 0.82-4.71; p = 0.13). Surprisingly, GSTT1 null genotype was significantly associated with the risk of CML in males (OR 95% CI, 5, 1.25-20.1; p = 0.023). The combined GSTM1 present/GSTT1 null genotype was found to have a limited effect against the risk of CML (OR 95% CI, 0.3, 0.08-0.99; p = 0.049). Our findings have shown that GSTT1 null genotype might be a risk factor of CML in males. While, GSTT1 present genotype might be considered as protective against CML. However, further studies with a large sample size are needed to confirm our findings.
慢性髓系白血病（CML）与大多数癌症一样，是遗传或非遗传因素之间复杂相互作用的结果。接触内源性或外源性异生物素会降低个体的解毒活性，从而构成患癌风险。已知谷胱甘肽S-转移酶（GSTs）基因多态性会影响异生物素的解毒作用。因此，我们开展了一项病例对照研究，92例慢性髓系白血病患者（平均年龄±标准差，40.62±12.7岁）和93名健康非亲属对照（平均年龄±标准差，41.38±13.4岁）参与其中。通过多重聚合酶链反应确定GSTM1和GSTT1基因型。采用逻辑回归评估GSTM1和GSTT1缺失基因型与慢性髓系白血病之间以及联合基因型与慢性髓系白血病之间的可能联系。患者中GSTM1缺失基因型频率略高于对照组（48.9%对40.9%），但与慢性髓系白血病无关（比值比95%置信区间，1.4, 0.78 - 2.48；p = 0.271）。此外，患者和对照组之间GSTT1缺失基因型频率呈现相似趋势（17.4%对9.7%；比值比95%置信区间，1.97, 0.82 - 4.71；p = 0.13）。令人惊讶的是，GSTT1缺失基因型与男性慢性髓系白血病风险显著相关（比值比95%置信区间，5, 1.25 - 20.1；p = 0.023）。发现GSTM1存在/GSTT1缺失联合基因型对慢性髓系白血病风险的影响有限（比值比95%置信区间，0.3, 0.08 - 0.99；p = 0.049）结果表明，GSTT1缺失基因型可能是男性慢性髓系白血病的一个风险因素。而GSTT1存在基因型可能被认为对慢性髓系白血病有保护作用。然而，需要进一步开展大样本研究来证实我们的发现。
