Grudny Jacek, Kołakowski Jacek, Kruszewski Marcin, Szopiński Janusz, Sliwiński Paweł, Wiatr Elżbieta, Winek Jolanta, Załęska Jolanta, Zych Jacek, Roszkowski-Śliż Kazimierz
Third Department of Lung Diseases, Institute of Tuberculosis and Lung Diseases, ul. Płocka 26, Warsaw.
Pneumonol Alergol Pol. 2013;81(4):308-18.
Recent studies have shown an increased risk of lung cancer in patients with bronchial obstructive changes, including patients with COPD. It seems that there are common factors of pathogenesis of both diseases associated with oxidative stress. In the present paper the genes linked to the repair of oxidative damage of DNA, associated with cancer, of iron metabolism and coding proteolytic enzymes were assessed.
The study was conducted in two groups of patients: 53 patients with non-small cell lung cancer and chronic obstructive pulmonary disease, and 54 patients only with chronic obstructive pulmonary disease. The polymorphisms of the single nucleotide were determined in the case of the majority of genes using the PCR-RFLP method. The statistical analysis of quantitative variables was executed using the Mann-Withney U-test and the test of medians; the analysis of genetic variables was executed using the chi² test.
Regarding the polymorphisms of genes involved in iron metabolism, statistically significant differences between the two groups have been demonstrated only in the case of haptoglobin gene HP1/2. A higher incidence of form 1/1 was found in patients with COPD and a higher incidence of form 1/2 in patients with lung cancer and COPD. Analysis of gene polymorphisms of proteolytic enzymes and inhibitors of the enzyme gene showed statistically significant differences between the two groups only for the MMP3 gene 6A/5A. In the case of the MMP12 gene polymorphism (A-82G) a tendency toward differences in the occurrence of specific alleles was identified.
These results indicate that patients with coincidence of COPD and lung cancer have disorders of the genes involved in iron metabolism, and they have different genetic polymorphisms of proteolytic enzymes comparing to COPD patients.
近期研究表明，包括慢性阻塞性肺疾病（COPD）患者在内，支气管阻塞性改变患者患肺癌的风险增加。似乎这两种疾病的发病机制存在与氧化应激相关的共同因素。在本文中，对与DNA氧化损伤修复、癌症相关、铁代谢以及编码蛋白水解酶的基因进行了评估。
该研究在两组患者中进行：53例非小细胞肺癌合并慢性阻塞性肺疾病患者，以及54例仅患有慢性阻塞性肺疾病的患者。对于大多数基因，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法测定单核苷酸多态性。使用曼-惠特尼U检验和中位数检验对定量变量进行统计分析；使用卡方检验对基因变量进行分析。
关于参与铁代谢的基因多态性，仅在触珠蛋白基因HP1/2的情况下，两组之间显示出统计学上的显著差异。在COPD患者中发现1/1型的发生率较高，而在肺癌合并COPD患者中1/2型的发生率较高。对蛋白水解酶及其酶基因抑制剂的基因多态性分析表明，仅MMP3基因6A/5A在两组之间存在统计学上的显著差异。在MMP12基因多态性（A-82G）的情况下，确定了特定等位基因出现存在差异的趋势。
这些结果表明，COPD合并肺癌患者存在参与铁代谢的基因紊乱，并且与COPD患者相比，他们具有不同的蛋白水解酶基因多态性。
