Role of VEGFA gene polymorphisms in colorectal cancer patients who treated with bevacizumab

Abstract

Objectives: This study aimed to explore the effects of vascular endothelial growth factor A (VEGFA) gene polymorphisms (rs699947 and rs833061) on Bevacizumab (BEV) treatment in colorectal cancer (CRC) patients.

Methods: 125 CRC cases receiving BEV plus FOLFIRI treatment were recruited in this study. VEGFA polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Correlation of VEGFA gene polymorphisms with the response rate and progression free survival (PFS) was evaluated. Multivariate analyses were performed to estimate the effects of VEGFA polymorphisms on the therapeutic effects of BEV treatment in CRC patients.

Results: Rs699947 variants did not show significant association with BEV treatment. For rs833061 analysis, TT and TC genotype carriers had significantly higher ORR (objective response rate) than CC carriers (P=0.048 and P=0.021, respectively). Moreover, TT carriers underwent a well DCR (disease control rate) compared to CC carriers (P=0.002). PFS time also showed obvious correlation with rs833061 polymorphism (log rank test, P=0.002). Multivariate analyses demonstrated that TT and TC genotypes of rs833061 polymorphism were significantly correlated with enhanced therapeutic effects and prolonged PFS in CRC patients.

Conclusion: VEGFA rs833061 polymorphism is significantly associated with the therapeutic efficiency of bevacizumab in CRC patients.

Keywords: VEGFA; bevacizumab; colorectal cancer; polymorphisms.

Figure 1. Effects of rs699947 and rs833061 polymorphisms on PFS among CRC patients receiving BEV treatments

There was no significant association between rs699947 polymorphism with PFC (log rank test, P=0.392). While rs833061 polymorphism showed obvious correlation with PFS among the study population (log rank test, P=0.002). TT carriers had a significantly better PFS than CC carriers (log rank test, P=0.001), while patients carrying TC genotype had obviously better PFS than those carrying CC genotype (log rank test, P=0.013). There was no remarkable difference between TT carriers and TC carriers (log rank test, P=0.126). The significant level was adjusted by Bonferroni method, α=0.017.