title: Polymorphisms in EGFR and VEGF contribute to non-small-cell lung cancer survival in a Chinese population.
abstract: Over the last decades, combined chemotherapies that inhibit different signalling pathways together have been demonstrated to be more effective to treat the non-small-cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR) and the vascular endothelium growth factor (VEGF) are two key targets. Polymorphisms in EGFR and VEGF genes have been identified to be associated with therapy-response and cancer survival. In this study, we hypothesized that single-nucleotide polymorphisms (SNPs) of EGFR and VEGF genes are associated with NSCLC patients' survival in Chinese. Therefore, we screened and genotyped 54 potentially functional SNPs as well as tagging SNPs in these two genes using Illumina Golden Gate platform in 568 NSCLC patients. We found that subjects carrying EGFR rs3735061AA and rs6958497AG/GG genotypes survived significantly shorter time [median survival time (MST): 22.2 and 19.4 months, respectively] than those carrying rs3735061AG/GG (MST: 25.1 months) and rs6958497AA (MST: 25.9 months) (log-rank P = 0.015 for rs3735061 and log-rank P = 0.028 for rs6958497). However, subjects carrying EGFR rs759165AG/AA genotypes survived significantly longer (MST: 38.7 months) than those carrying rs759165GG genotype (MST: 24.7 months) (log-rank P = 0.024). Multivariate Cox regression analyses showed that the genotypes of rs3735061AA and rs6958497AG/GG were associated with a significantly increased risk of death for NSCLC [hazard ratio (HR) = 2.82, 95% confidence interval (CI) = 1.66-4.78 for rs3735061AA and HR = 1.69, 95% CI = 1.26-2.28 for rs6958497AG/GG], whereas the rs759165AG/AA were associated with a 44% significantly decreased risk of death of NSCLC (HR = 0.56, 95% CI = 0.39-0.83). Stepwise COX regression analyses suggested that EGFR rs373506, rs759165 and rs6958497 may be independent candidate biomarkers to predict NSCLC survival in this population.
authors.affiliation: Department of Epidemiology and Biostatistics, Cancer Center, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Shu
authors.forename: Shiyang
authors.initials: S
authors.lastname: Pan
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Wenping
authors.initials: W
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Zhang
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002681:China; D015331:Cohort Studies; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D066246:ErbB Receptors