Sasaki Hidefumi, Suzuki Ayumi, Shitara Masayuki, Hikosaka Yu, Okuda Katsuhiro, Moriyama Satoru, Yano Motoki, Fujii Yoshitaka
Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
Biomed Rep. 2013 May;1(3):484-488. doi: 10.3892/br.2013.83. Epub 2013 Mar 19.
The metabolism of xenobiotics plays a fundamental role in smoking-related lung function loss and the development of pulmonary disease. An NRF2-dependent response is a key protective mechanism against oxidative stress. In the present study, we evaluated the effect of single nucleotide polymorphisms in NRF2 genes on the level of forced expiratory volume in one second (FEV1) in lung cancers of smokers. We genotyped the status of NRF2 gene polymorphisms in 209 surgically treated lung cancer cases of smokers using TaqMan polymerase chain reaction (PCR). The results demonstrated the mean FEV1 in patients with rs2364723 C/C, C/G and G/G to be 2143.9, 2294.2 and 2335.4 ml, respectively, and there was a tendency towards lower FEV1 in C/C phenotype (P=0.0944). The mean FEV1 was significantly lower in the C/C phenotype (2143.9±566.0 ml) compared to C/G or G/G (2308.9±642.9 ml, P=0.05). The mean FEV1 in patients with rs6726395 A/A, G/A and G/G was 66.7, 71.2 and 72.3%, respectively, and there was a significant difference between A/A and G/G phenotype (P=0.043). A tendency towards a lower mean FEV1 in A/A phenotype (66.7±11.7%) was observed when compared to A/G or G/G (71.9±10.7%, P=0.07). This study demonstrated that an NRF2-dependent response to cigarette smoking has the potential to affect FEV1 decrease in a lung cancer population. In conclusion, the results have shown that NRF2 genetic changes may play a role in FEV1 loss in smokers with lung cancer.
外源性物质的代谢在吸烟相关的肺功能丧失和肺部疾病的发展中起着重要作用。NRF2依赖的反应是对抗氧化应激的关键保护机制。在本研究中，我们评估了NRF2基因单核苷酸多态性对吸烟者肺癌患者一秒用力呼气量（FEV1）水平的影响。我们使用TaqMan聚合酶链反应（PCR）对209例接受手术治疗的吸烟肺癌患者的NRF2基因多态性状态进行了基因分型。结果显示，rs2364723 C/C、C/G和G/G基因型患者的平均FEV1分别为2143.9、2294.2和2335.4 ml，C/C基因型患者的FEV1有降低趋势（P = 0.0944）。与C/G或G/G基因型（2308.9±642.9 ml）相比，C/C基因型患者的平均FEV1显著降低（2143.9±566.0 ml，P = 0.05）。rs6726395 A/A、G/A和G/G基因型患者的平均FEV1分别为66.7%、71.2%和72.3%，A/A和G/G基因型之间存在显著差异（P = 0.043）。与A/G或G/G基因型（71.9±10.7%）相比，A/A基因型患者的平均FEV1有降低趋势（66.7±11.7%，P = 0.07）。本研究表明，NRF2依赖的对吸烟的反应有可能影响肺癌人群中FEV1的下降。总之，结果表明NRF2基因变化可能在吸烟肺癌患者的FEV1丧失中起作用。
