Pharmacogenetic interaction analysis of VEGFR-2 and IL-8 polymorphisms in advanced breast cancer patients treated with paclitaxel and bevacizumab

AIM: To investigate pharmacogenetic interactions among VEGF-A, VEGFR-2, IL-8,HIF-1??, EPAS-1 and TSP-1 SNPs and their role on progression-free survival in apopulation of metastatic breast cancer patients treated with bevacizumab incombination with first-line paclitaxel.PATIENTS & METHODS: Analyses were performed on germline DNA obtained from bloodsamples and SNPs were investigated by real-time polymerase chain reactiontechnique. The multifactor dimensionality reduction methodology was applied toinvestigate the interaction between SNPs.RESULTS: One hundred and thirteen patients were enrolled from eight ItalianOncology Units ( clinicaltrial.gov : NCT01935102). The multifactor dimensionalityreduction software provided two pharmacogenetic interaction profiles consistingof the combination between specific VEGFR-2 rs11133360 and IL-8 rs4073 genotypes.The median progression-free survival was 14.1 months (95% CI: 11.4-16.8) and 10.2months (95% CI: 8.8-11.5) for the favorable and the unfavorable genetic profile, respectively (HR: 0.44, 95% CI: 0.29-0.66, p < 0.0001).CONCLUSION: The pharmacogenetic statistical interaction between VEGFR-2rs11133360 and IL-8 rs4073 genotypes may identify a population of patients with abetter outcome.