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.
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.
Pharmacogenetic interaction analysis of VEGFR-2 and IL-8 polymorphisms in advanced breast cancer patients treated with paclitaxel and bevacizumab / G. Allegrini, L. Coltelli, P. Orlandi, A. Fontana, A. Camerini, A. Ferro, M. Cazzaniga, V. Casadei, S. Lucchesi, E. Bona, M. Di Lieto, I. Pazzagli, F. Villa, D. Amoroso, M. Scalese, G. Arrighi, S. Molinaro, A. Fioravanti, C. Finale, R. Triolo, T. DI DESIDERO, S. Donati, L. Marcucci, O. Goletti, M. DEL RE, B. Salvadori, I. Ferrarini, R. Danesi, A. Falcone, G. Bocci. - In: PHARMACOGENOMICS. - ISSN 1462-2416. - 15:16(2014), pp. 1985-1999. [10.2217/pgs.14.140]
Pharmacogenetic interaction analysis of VEGFR-2 and IL-8 polymorphisms in advanced breast cancer patients treated with paclitaxel and bevacizumab
R. Danesi;
2014
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.
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