title: Pharmacogenetic interaction analysis of VEGFR-2 and IL-8 polymorphisms in advanced breast cancer patients treated with paclitaxel and bevacizumab.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  The pharmacogenetic statistical interaction between VEGFR-2 rs11133360 and IL-8 rs4073 genotypes may identify a population of patients with a better outcome.
authors.affiliation: Division of Medical Oncology, Pontedera Hospital, Pisa, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Allegrini
authors.forename: Luigi
authors.initials: L
authors.lastname: Coltelli
authors.forename: Paola
authors.initials: P
authors.lastname: Orlandi
authors.forename: Andrea
authors.initials: A
authors.lastname: Fontana
authors.forename: Andrea
authors.initials: A
authors.lastname: Camerini
authors.forename: Antonella
authors.initials: A
authors.lastname: Ferro
authors.forename: Marina
authors.initials: M
authors.lastname: Cazzaniga
authors.forename: Virginia
authors.initials: V
authors.lastname: Casadei
authors.forename: Sara
authors.initials: S
authors.lastname: Lucchesi
authors.forename: Eleonora
authors.initials: E
authors.lastname: Bona
authors.forename: Marco
authors.initials: M
authors.lastname: Di Lieto
authors.forename: Ilaria
authors.initials: I
authors.lastname: Pazzagli
authors.forename: Federica
authors.initials: F
authors.lastname: Villa
authors.forename: Domenico
authors.initials: D
authors.lastname: Amoroso
authors.forename: Marco
authors.initials: M
authors.lastname: Scalese
authors.forename: Giada
authors.initials: G
authors.lastname: Arrighi
authors.forename: Sabrina
authors.initials: S
authors.lastname: Molinaro
authors.forename: Anna
authors.initials: A
authors.lastname: Fioravanti
authors.forename: Chiara
authors.initials: C
authors.lastname: Finale
authors.forename: Renza
authors.initials: R
authors.lastname: Triolo
authors.forename: Teresa
authors.initials: T
authors.lastname: Di Desidero
authors.forename: Sara
authors.initials: S
authors.lastname: Donati
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Marcucci
authors.forename: Orlando
authors.initials: O
authors.lastname: Goletti
authors.forename: Marzia
authors.initials: M
authors.lastname: Del Re
authors.forename: Barbara
authors.initials: B
authors.lastname: Salvadori
authors.forename: Ilaria
authors.initials: I
authors.lastname: Ferrarini
authors.forename: Romano
authors.initials: R
authors.lastname: Danesi
authors.forename: Alfredo
authors.initials: A
authors.lastname: Falcone
authors.forename: Guido
authors.initials: G
authors.lastname: Bocci
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics*; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D019700:Thrombospondin 1 / Q000235:genetics; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D051792:Basic Helix-Loop-Helix Proteins; D000068258:Bevacizumab; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016209:Interleukin-8; D017239:Paclitaxel; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human; C467484:VEGFA protein, human; C000588866:KDR protein, human
keywords: advanced breast cancer; angiogenesis; bevacizumab; first-line chemotherapy; multifactor dimensionality reduction methodology; paclitaxel; pharmacogenetics; single nucleotide polymorphisms