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 a population of metastatic breast cancer patients treated with bevacizumab in combination with first-line paclitaxel. PATIENTS & METHODS: Analyses were performed on germline DNA obtained from blood samples and SNPs were investigated by real-time polymerase chain reaction technique. The multifactor dimensionality reduction methodology was applied to investigate the interaction between SNPs. RESULTS: One hundred and thirteen patients were enrolled from eight Italian Oncology Units ( clinicaltrial.gov : NCT01935102). The multifactor dimensionality reduction software provided two pharmacogenetic interaction profiles consisting of 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 10.2 months (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-2 rs11133360 and IL-8 rs4073 genotypes may identify a population of patients with a better outcome.
|Autori:||Allegrini G; Coltelli L; Orlandi P; Fontana A; Camerini A; Ferro A; Cazzaniga M; Casadei V; Lucchesi S; Bona E; Di Lieto M; Pazzagli I; Villa F; Amoroso D; Scalese M; Arrighi G; Molinaro S; Fioravanti A; Finale C; Triolo R; Di Desidero T; Donati S; Marcucci L; Goletti O; Del Re M; Salvadori B; Ferrarini I; Danesi R; Falcone A; Bocci G|
|Titolo:||Pharmacogenetic interaction analysis of VEGFR-2 and IL-8 polymorphisms in advanced breast cancer patients treated with paclitaxel and bevacizumab.|
|Anno del prodotto:||2014|
|Digital Object Identifier (DOI):||10.2217/pgs.14.140|
|Appare nelle tipologie:||1.1 Articolo in rivista|