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

• DOI: 10.2217/pgs.14.140
• Publication Date: 2014-12-19T07:56:37Z
• Authors: Giacomo Allegrini; Luigi Coltelli; Paola Orlandi; Andrea Fontana; Andrea Camerini; Antonella Ferro; Marina Cazzaniga; Virginia Casadei; Sara Lucchesi; Eleonora Bona; Marco Di Lieto; Ilaria Pazzagli; Federica Villa; Domenico Amoroso; Marco Scalese; Giada Arrighi; Sabrina Molinaro; Anna Fioravanti; Chiara Finale; Renza Triolo; Teresa Di Desidero; Sara Donati; Lorenzo Marcucci; Orlando Goletti; Marzia Del Re; Barbara Salvadori; Ilaria Ferrarini; Romano Danesi; Alfredo Falcone; Guido Bocci
• Keywords: Vascular Endothelial Growth Factor A; 0301 basic medicine; Paclitaxel; pharmacogenetics; VEGF; IL-8; bevacizumab; Breast Neoplasms; bevacizumab; Antibodies, Monoclonal, Humanized; Polymorphism, Single Nucleotide; Disease-Free Survival; Thrombospondin 1; angiogenesis; paclitaxel; single nucleotide polymorphisms; 03 medical and health sciences; multifactor dimensionality reduction methodology; Basic Helix-Loop-Helix Transcription Factors; Humans; Genetic Association Studies; pharmacogenetics; Neoplasm Staging; advanced breast cancer; Interleukin-8; Hypoxia-Inducible Factor 1, alpha Subunit; Vascular Endothelial Growth Factor Receptor-2; 3. Good health; Bevacizumab; first-line chemotherapy; Treatment Outcome; Pharmacogenetics; advanced breast cancer; angiogenesis; bevacizumab; first-line chemotherapy; multifactor dimensionality reduction methodology; paclitaxel; pharmacogenetics; single nucleotide polymorphisms;; Female

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.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.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).The pharmacogenetic statistical interaction between VEGFR-2 rs11133360 and IL-8 rs4073 genotypes may identify a population of patients with a better outcome.