Tkácová Ruzena, Salagovic Ján, Ceripková Marianna, Tkác Ivan, Stubna Ján, Kalina Ivan
Department of Tuberculosis and Respiratory Medicine, Faculty of Medicine, P. J. Safárik University, Kosice, Slovakia.
Wien Klin Wochenschr. 2004 Feb 28;116(4):131-4. doi: 10.1007/BF03040750.
Oxidative stress contributes to the development of both lung cancer and chronic obstructive pulmonary disease (COPD). Antioxidative enzymes may protect against such damage. We hypothesized that genetic variations in glutathione S-transferase M1 and/or T1 genes (GSTM1 and GSTT1, respectively) may influence susceptibility to COPD in patients with non-small-cell lung cancer.
The polymorphisms in GSTM1 and GSTT1 genes were examined in 110 patients (age: 63+/-1 years) with newly diagnosed non-small-cell lung cancer using the polymerase chain reaction. Respiratory function was assessed by bodyplethysmography.
In the GSTM1 null (-/-) genotype, both FEV1 and FEV1/FVC were significantly lower than in the GSTM1 plus genotype (GSTM1 -/+ or +/+) (75.8+/-2.5 versus 86.6+/-3.6%, p<0.02; 69.1+/-1.6 versus 77.0+/-2.4, p<0.01, respectively). Among the patients with GSTM1 null genotype, 49% suffered from COPD as opposed to 21% of patients with GSTM1 plus genotype. In contrast, no differences were seen in FEV1 or FEV1/FVC when comparing patients with GSTT1 null genotype and GSTT1 plus genotype (81.4+/-4.9 versus 79.3+/-2.3, p=NS; 71.1+/-2.9 versus 72.2+/-1.6, p=NS). Multiple stepwise regression analysis identified the GSTM1 genotype (p<0.02) as a significant independent predictor of FEV1 in this group of patients.
The present study suggests that in patients with non-small-cell lung cancer the presence of at least one active allele in GSTM1 has a protective effect against the development of COPD.
氧化应激在肺癌和慢性阻塞性肺疾病（COPD）的发生发展中均起作用。抗氧化酶可能预防此类损伤。我们推测谷胱甘肽S-转移酶M1和/或T1基因（分别为GSTM1和GSTT1）的基因变异可能影响非小细胞肺癌患者患COPD的易感性。
采用聚合酶链反应检测110例新诊断的非小细胞肺癌患者（年龄：63±1岁）的GSTM1和GSTT1基因多态性。通过体容积描记法评估呼吸功能。
在GSTM1无效（-/-）基因型中，FEV1和FEV1/FVC均显著低于GSTM1阳性基因型（GSTM1 -/+或+/+）（分别为75.8±2.5%对86.6±3.6%，p<0.02；69.1±1.6对77.0±2.4，p<0.01）。在GSTM1无效基因型患者中，49%患有COPD，而GSTM1阳性基因型患者中这一比例为21%。相比之下，比较GSTT1无效基因型和GSTT1阳性基因型患者时，FEV1或FEV1/FVC未见差异（81.4±4.9对79.3±2.3，p=无显著性差异；71.1±2.9对72.2±1.6，p=无显著性差异）。多步逐步回归分析确定GSTM1基因型（p<0.02）是该组患者FEV1的显著独立预测因子。
本研究提示，在非小细胞肺癌患者中，GSTM1中至少存在一个活性等位基因对COPD的发生具有保护作用。
