title: Polymorphisms of NRF2 gene correlated with decreased FEV1 in lung cancers of smokers.
abstract: 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.
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shitara
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hikosaka
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Okuda
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Moriyama
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Yano
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujii
keywords: NRF2; forced expiratory volume in 1 second; nuclear factor (erythroid derived 2)-like 2; polymorphism; smoker