Pharmacogenetic interaction analysis of VEGFR-2 and IL-8 polymorphisms in advanced breast cancer patients treated with paclitaxel and bevacizumab. (December 2014)

• Record Type: Journal Article
• Authors: Allegrini, Giacomo; Coltelli, Luigi; Orlandi, Paola; Fontana, Andrea; Camerini, Andrea; Ferro, Antonella; Cazzaniga, Marina; Casadei, Virginia; Lucchesi, Sara; Bona, Eleonora; Di Lieto, Marco; Pazzagli, Ilaria; Villa, Federica; Amoroso, Domenico; Scalese, Marco; Arrighi, Giada; Molinaro, Sabrina; Fioravanti, Anna; Finale, Chiara; Triolo, Renza; Di Desidero, Teresa; Donati, Sara; Marcucci, Lorenzo; Goletti, Orlando; Del Re, Marzia; Salvadori, Barbara; Ferrarini, Ilaria; Danesi, Romano; Falcone, Alfredo; Bocci, Guido
• Is Part Of: Pharmacogenomics. Volume 15:Number 16(2014)
• Page Start: 1985
• Page End: 1999
• Publication Date: 2014-12
• Subjects: advanced breast cancer -- angiogenesis -- bevacizumab -- first-line chemotherapy -- multifactor dimensionality reduction methodology -- paclitaxel -- pharmacogenetics -- single nucleotide polymorphisms; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs.14.140
• Languages: English
• ISSNs: 1462-2416

Abstract

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.