Polymorphisms of the vascular endothelial growth factor gene and severe radiation pneumonitis in non‐small cell lung cancer patients treated with definitive radiotherapy

摘要

Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis and lung cancer progression. We hypothesized that VEGF polymorphisms may modulate the risk of radiation pneumonitis (RP) in non‐small cell lung cancer (NSCLC) patients treated with definitive radiotherapy. We genotyped three potentially functional VEGF single nucleotide polymorphisms (&460 T > C [rs833061], &634 G > C [rs2010963] and +936 C > T [rs3025039]) and estimated the associations of their genotypes and haplotypes with severe radiation pneumonitis (RP ≥grade 3) in 195 NSCLC patients. We found that the style="italic-in-any-context">VEGF genotypes of rs2010963 and rs3025039 single nucleotide polymorphisms as well as the &460 style="fixed-case">C/&634 style="fixed-case">G/+936 style="fixed-case">C haplotype were predictors of style="fixed-case">RP development (adjusted hazard ratio [adj style="fixed-case">HR] = 2.33, 95% confidence interval [ style="fixed-case">CI], 1.01–5.37, P = 0.047 for style="fixed-case">CC vs style="fixed-case">GG genotypes; adj style="fixed-case">HR = 28.13, 95% style="fixed-case">CI, 5.24–151.02, P < 0.001 for style="fixed-case">TT vs style="fixed-case">CC genotypes; and adj style="fixed-case">HR = 2.51, 95% style="fixed-case">CI, 1.27–4.98, P = 0.008 for style="fixed-case">T‐C‐T vs style="fixed-case">C‐G‐C haplotypes). In addition, there was a trend towards reduced style="fixed-case">RP risk in patients carrying an increased number of protective style="fixed-case"> style="italic-in-any-context">VEGF genotypes. Our data suggest that style="fixed-case"> style="italic-in-any-context">VEGF polymorphisms can modulate the risk of radiation pneumonitis in style="fixed-case">NSCLC patients treated with definitive radiotherapy. Large and independent studies are needed to confirm our findings. (Cancer Sci 2012; 103: 945–950)