title: Effect of vascular endothelial growth factor polymorphisms on survival in advanced-stage non-small-cell lung cancer.
abstract: Polymorphisms have been identified in the vascular endothelial growth factor (VEGF) gene that may affect VEGF production. We hypothesized that such polymorphisms may correlate with survival outcomes among advanced-stage non-small-cell lung cancer (NSCLC) patients. We evaluated the association between VEGF polymorphisms and overall survival among patients with advanced NSCLC who were treated with at least one cytotoxic regimen at Kyoto University Hospital between 2003 and 2008. We investigated the following VEGF polymorphisms: -460T > C (rs833061), +405G > C (rs2010963), +936C > T (rs3025039), -1154G > A (rs1570360), and -2578C > A (rs699947). Analyses of genotype associations with survival outcomes were performed using Cox proportional models, Kaplan-Meier methods, and the log-rank test. There were 126 patients and 80 deaths. On a Cox regression analysis of a current and former smoker (hazards ratio [HR], 1.422; 95% confidence interval [CI], 1.111-1.859; P = 0.0046), poor performance status (PS) (HR, 2.524; 95% CI, 1.483-3.827; P = 0.0019), the VEGF -460CC genotype (HR, 1.719; 95% CI, 1.166-2.390; P = 0.0084), VEGF -1154AA and AG genotypes (HR, 1.482; 95% CI, 1.144-1.897; P = 0.0034), and VEGF -2578AA genotype (HR, 1.797; 95% CI, 1.219-2.495; P = 0.0047) had a significant prognostic effect on survival based on univariate analysis. Based on multivariate analysis of a current and former smoker (HR, 1.407; 95% CI, 1.095-1.840; P = 0.0070), poor PS (HR, 2.249; 95% CI, 1.309-3.468; P = 0.0058), and the VEGF -1154AA and AG genotypes (HR, 1.419; 95% CI, 1.033-1.901; P = 0.0316) were significant independent prognostic factors for survival. In this study, polymorphisms in VEGF may affect survival in advanced NSCLC.
authors: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. masago@kuhp.kyoto-u.ac.jp
authors: Katsuhiro
authors: K
authors: Masago
authors: Shiro
authors: S
authors: Fujita
authors: Yung Haku
authors: YH
authors: Kim
authors: Yukimasa
authors: Y
authors: Hatachi
authors: Akiko
authors: A
authors: Fukuhara
authors: Hiroki
authors: H
authors: Nagai
authors: Kaoru
authors: K
authors: Irisa
authors: Masataka
authors: M
authors: Ichikawa
authors: Tadashi
authors: T
authors: Mio
authors: Michiaki
authors: M
authors: Mishima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A