title: Genetic polymorphisms in oxidative stress-related genes are associated with clinical outcome in patients with advanced non-small cell lung cancer receiving tyrosine kinase inhibitors.
abstract: Many types of cancer have high antioxidant capacity that effectively scavenges reactive oxygen species and thus protect cancer cells against oxidative damage. The aim of this study was to examine the effect of 20 single nucleotide polymorphisms (SNPs) in 20 oxidative stress-related genes on clinical outcome in 219 patients with advanced non-small cell lung cancer (NSCLC) who were treated with EGFR tyrosine kinase inhibitors (TKIs). We assessed the associations of SNPs with prognosis in all patients as well as stratified by clinical characteristics. Three SNP (rs1695, rs2333227 and rs699512) were significantly associated with overall survival (OS). In a multivariate analysis, rs1695 AA and rs2333227 AG/GG genotypes were identified as independent prognostic factors for poor OS. Stratification analyses revealed that these 3 SNPs remained significantly associated with OS. Furthermore, there was a strong gene-dosage effect of these 3 SNPs on OS that patients with increasing number of unfavorable genotypes had significantly increased death risk. In conclusion, our findings provide the first evidence that genetic variants in oxidative stress-related genes may influence treatment outcome in advanced NSCLC patients receiving EGFR TKIs.
authors.affiliation: Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiaotong University Shanghai, China.
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Surgical Oncology, Quanzhou First Hospital Quanzhou, Fujian, China.
authors.forename: Qunxiong
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Department of Surgical Oncology, Quanzhou First Hospital Quanzhou, Fujian, China.
authors.forename: Chongren
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Surgical Oncology, Taizhou Central Hospital Taizhou, Zhejiang, China.
authors.forename: Chunya
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Surgical Oncology, Quanzhou First Hospital Quanzhou, Fujian, China.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Surgical Oncology, Taizhou Central Hospital Taizhou, Zhejiang, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Thoracic Surgery, Taizhou Hospital Taizhou, Zhejiang, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Taizhou Hospital Taizhou, Zhejiang, China.
authors.forename: Min
authors.initials: M
authors.lastname: Kong
authors.affiliation: Department of Surgical Oncology, Quanzhou First Hospital Quanzhou, Fujian, China.
authors.forename: Shaoying
authors.initials: S
authors.lastname: Ke
authors.affiliation: Department of Surgical Oncology, Quanzhou First Hospital Quanzhou, Fujian, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Taizhou Hospital Taizhou, Zhejiang, China.
authors.forename: Baofu
authors.initials: B
authors.lastname: Chen
authors.affiliation: Shanghai Engineering Center for Molecular Medicine, National Engineering Center for Biochip at Shanghai Shanghai, China.
authors.forename: Haihui
authors.initials: H
authors.lastname: Sheng
authors.affiliation: Department of Thoracic Surgery, Taizhou Central Hospital Taizhou, Zhejiang, China.
authors.forename: Xuelin
authors.initials: X
authors.lastname: Zhang
keywords: Tyrosine kinase inhibitor; biliverdin reductase A; glutathione S-transferases P1; lung cancer; myeloperoxidase; oxidative stress; single nucleotide polymorphism