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Pharmacogenetic Interaction Analysis of VEGFR-2 and IL-8 Polymorphisms in Advanced Breast Cancer Patients Treated with Paclitaxel and Bevacizumab

2014; Future Medicine; Volume: 15; Issue: 16 Linguagem: Inglês

10.2217/pgs.14.140

1744-8042

Giacomo Allegrini, Luigi Coltelli, Paola Orlandi, Andrea Fontana, Andrea Camerini, Antonella Ferro, Marina Elena Cazzaniga, Virginia Casadei, Sara Lucchesi, Eleonora Bona, Marco Di Lieto, Ilaria Pazzagli, Federica Villa, D. Amoroso, Marco Scalese, Giada Arrighi, Sabrina Molinaro, Anna Fioravanti, Chiara Finale, R Triolo, Teresa Di Desidero, Sara Donati, Lorenzo Marcucci, Orlando Goletti, Marzia Del Re, B. Salvadori, I. Ferrarini, Romano Danesi, Alfredo Falcone, Guido Bocci,

Cancer Cells and Metastasis

Aim: To investigate pharmacogenetic interactions among VEGF-A, VEGFR-2, IL-8, HIF-1α, 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.