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

Patrizia Ferroni; Raffaele Palmirotta; Silvia Riondino; Maria Laura De Marchis; Antonella Nardecchia; Vincenzo Formica; Fiorella Guadagni; Mario Roselli

doi:10.1160/TH15-03-0259

Thrombosis and Haemostasis, Table of Contents

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

¹University San Raffaele Rome, Italy

²Interinstitutional Multidisciplinary BioBank (BioBIM), IRCCS San Raffaele Pisana, Rome, Italy

,

Raffaele Palmirotta

¹University San Raffaele Rome, Italy

²Interinstitutional Multidisciplinary BioBank (BioBIM), IRCCS San Raffaele Pisana, Rome, Italy

,

Silvia Riondino

²Interinstitutional Multidisciplinary BioBank (BioBIM), IRCCS San Raffaele Pisana, Rome, Italy

³Medical Oncology, Department of Systems Medicine, Tor Vergata Clinical Centre, University of Rome “Tor Vergata”, Rome, Italy

,

Maria Laura De Marchis

²Interinstitutional Multidisciplinary BioBank (BioBIM), IRCCS San Raffaele Pisana, Rome, Italy

,

Antonella Nardecchia

³Medical Oncology, Department of Systems Medicine, Tor Vergata Clinical Centre, University of Rome “Tor Vergata”, Rome, Italy

,

Vincenzo Formica

³Medical Oncology, Department of Systems Medicine, Tor Vergata Clinical Centre, University of Rome “Tor Vergata”, Rome, Italy

,

Fiorella Guadagni^§

¹University San Raffaele Rome, Italy

²Interinstitutional Multidisciplinary BioBank (BioBIM), IRCCS San Raffaele Pisana, Rome, Italy

,

Mario Roselli^§

³Medical Oncology, Department of Systems Medicine, Tor Vergata Clinical Centre, University of Rome “Tor Vergata”, Rome, Italy

› Author Affiliations

Abstract

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

Full Text

References

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