Stankovic M M, Nestorovic A R, Tomovic A M, Petrovic-Stanojevic N D, Andjelic-Jelic M S, Dopudja-Pantic V B, Nagorni-Obradovic Lj M, Mitic-Milikic M M, Radojkovic D P
Institute of Molecular Genetics and genetic Engineering, Belgrade, Serbia.
Neoplasma. 2009;56(4):348-52. doi: 10.4149/neo_2009_04_348.
Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are a major cause of morbidity and mortality worldwide. In both diseases airways inflammation plays an important role. Functional promoter polymorphism, at the position -308, of tumor necrosis factor (TNF)-alpha represents attractive potential susceptibilty marker for both diseases. In order to investigate the role of this polymorphism in COPD and LC, a case-control study was performed. The patient groups consisted of 97 subjects with COPD and 70 subjects with LC, while the control group encompassed 102 subjects. Results of our study showed significant decrease of heterozygote for TNF-alpha-308 1/2 gene variant in COPD group in comparison to controls (p=0.043). According to our results heterozygous carriers of TNF-alpha-308 1/2 polymorphism had a2.3-fold decreased risk for COPD development (OR=0.44, 95%CI=0.20-0.97). In patients with lung cancer we also observed a trend of decreased distribution of TNF-alpha-308 1/2 heterozygotes, but statistical significance was not achieved. To our knowledge, this is the first study implicating decreased frequency of TNF-alpha-308 1/2 gene variant in patients with COPD and LC. Although these results need to be confirmed on larger cohort, they represent anew and interesting finding, not reported in other populations tested so far.
慢性阻塞性肺疾病（COPD）和肺癌（LC）是全球发病和死亡的主要原因。在这两种疾病中，气道炎症都起着重要作用。肿瘤坏死因子（TNF）-α基因-308位点的功能性启动子多态性是这两种疾病颇具吸引力的潜在易感标志物。为了研究这种多态性在COPD和LC中的作用，我们进行了一项病例对照研究。患者组包括97例COPD患者和70例LC患者，对照组包括102名受试者。我们的研究结果显示，与对照组相比，COPD组中TNF-α -308 1/2基因变异杂合子显著减少（p = 0.043）。根据我们的结果，TNF-α -308 1/2多态性的杂合子携带者患COPD的风险降低了2.3倍（OR = 0.44，95%CI = 0.20 - 0.97）。在肺癌患者中，我们也观察到TNF-α -308 1/2杂合子分布减少的趋势，但未达到统计学意义。据我们所知，这是第一项表明COPD和LC患者中TNF-α -308 1/2基因变异频率降低的研究。尽管这些结果需要在更大的队列中得到证实，但它们代表了一个新的有趣发现，在迄今为止测试的其他人群中尚未报道。
