Genotypes and haplotypes of the VEGF gene and survival in locally advanced non-small cell lung cancer patients treated with chemoradiotherapy

Abstract

Background: Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving in carcinogenesis, including lung cancer. We hypothesized that VEGF polymorphisms may affect survival outcomes among locally advanced non-small cell lung cancer (LA-NSCLC) patients.

Methods: We genotyped three potentially functional VEGF variants [-460 T > C (rs833061), -634 G > C (rs2010963), and +936 C > T (rs3025039)] and estimated haplotypes in 124 Caucasian patients with LA-NSCLC treated with definitive radiotherapy. We used Kaplan-Meier log-rank tests, and Cox proportional hazard models to evaluate the association between VEGF variants and overall survival (OS).

Results: Gender, Karnofsky's performance scores (KPS) and clinical stage seemed to influence the OS. The variant C genotypes were independently associated with significantly improved OS (CT+CC vs. TT: adjusted hazard ratio [HR] = 0.58; 95% confidence interval [CI] = 0.37-0.92, P = 0.022), compared with the VEGF -460 TT genotype.

Conclusions: Our study suggests that VEGF -460 C genotypes may be associated with a better survival of LA-NSCLC patients after chemoradiotherapy. Large studies are needed to confirm our findings.

Figure 1

Overall survival curves by selected host factors with an association of significance level. The P values were obtained from the unadjusted Log-rank test.

Figure 2

PCR-based restriction analysis of the VEGF SNPs shown on agarose electrophoresis.

Figure 3

Overall survival curves by genotypes of VEGF gene. The P values were obtained from the Cox model with adjustment for age, sex, smoking status, tumor histology, KPS score, tumor stage, use of chemotherapy and radiotherapy dose.