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Thromb Haemost 2016; 115(01): 143-151
DOI: 10.1160/TH15-03-0259
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH Schattauer

VEGF gene promoter polymorphisms and risk of VTE in chemotherapy-treated cancer patients

Patrizia Ferroni
1   University San Raffaele Rome, Italy
2   Interinstitutional Multidisciplinary BioBank (BioBIM), IRCCS San Raffaele Pisana, Rome, Italy
,
Raffaele Palmirotta
1   University San Raffaele Rome, Italy
2   Interinstitutional Multidisciplinary BioBank (BioBIM), IRCCS San Raffaele Pisana, Rome, Italy
,
Silvia Riondino
2   Interinstitutional Multidisciplinary BioBank (BioBIM), IRCCS San Raffaele Pisana, Rome, Italy
3   Medical Oncology, Department of Systems Medicine, Tor Vergata Clinical Centre, University of Rome “Tor Vergata”, Rome, Italy
,
Maria Laura De Marchis
2   Interinstitutional Multidisciplinary BioBank (BioBIM), IRCCS San Raffaele Pisana, Rome, Italy
,
Antonella Nardecchia
3   Medical Oncology, Department of Systems Medicine, Tor Vergata Clinical Centre, University of Rome “Tor Vergata”, Rome, Italy
,
Vincenzo Formica
3   Medical Oncology, Department of Systems Medicine, Tor Vergata Clinical Centre, University of Rome “Tor Vergata”, Rome, Italy
,
Fiorella Guadagni   §
1   University San Raffaele Rome, Italy
2   Interinstitutional Multidisciplinary BioBank (BioBIM), IRCCS San Raffaele Pisana, Rome, Italy
,
Mario Roselli   §
3   Medical Oncology, Department of Systems Medicine, Tor Vergata Clinical Centre, University of Rome “Tor Vergata”, Rome, Italy
› Author Affiliations Financial support: This study was partially supported by research funding from the European Social Fund, under the Italian Ministry of Education, University and Research PON03PE_00146_1/10 BIBIOFAR (CUP B88F12000730005) and by research funding from the European Regional Development Fund PO FESR 2007/2013 Linea di Intervento 4.1.1.1 – SIASOP (CUP G83F11000290004).
Further Information

Publication History

Received: 27 March 2015

Accepted after major revision: 10 July 2015

Publication Date:
22 November 2017 (online)

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Summary

Among the possible genetic contributors to cancer-related venous thromboembolism (VTE), vascular endothelial growth factor (VEGFA) could play an important role, as an imbalance of the VEGFA system (either disease-related or drug-induced) may result in a disturbance of vascular homeostasis. Thus, this study was designed to investigate the predictive role of eight different VEGFA gene promoter single nucleotide polymorphisms (SNPs) for a first VTE episode in cancer out-patients undergoing chemotherapy. To this purpose, VEGFA gene promoter polymorphisms were analysed in 297 cancer patients using polymerase chain reaction amplification and direct DNA sequencing analysis. One hundred forty unrelated healthy subjects from the same geographical area were also analysed in order to evaluate and compare genotype/haplotype frequencies in our ethnicity. VTE occurred in 26 (9 %) of cancer patients with a median time-to-event of 3.4 months. Association analyses showed that –1154G/A polymorphism was significantly associated with the risk of chemotherapy-triggered VTE, with the A allele exerting a protective role both in the overall population (hazard ratio [HR]: 0.21; 95 % confidence interval [CI]: 0.07–0.58) or in bevacizumab-treated metastatic patients (HR: 0.09, 95 %CI: 0.01–0.86) in whom VEGFA –1154AA genotype also conferred a reduced risk of early progression (HR: 0.58, 95 %CI: 0.34–0.98). These results suggest that VEGFA may represent a candidate gene contributing to VTE development in chemotherapy treated cancer patients and that –1154G/A SNP might provide useful clinical information on the efficacy and toxicity of bevacizumab in metastatic patients. Validation studies are needed for translation into clinical practice.

Note: This study has been presented in part at the Congress on Controversies in Thrombosis & Haemostasis, Berlin, Germany, October 30-November 1, 2014.

Keywords

Venous thromboembolism - chemotherapy - vascular endothelial growth factor - single nucleotide polymorphisms - risk prediction

§ Co-senior authors with equal contribution.


 

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