Vascular Endothelial Growth Factor Pathway Polymorphisms as Prognostic and Pharmacogenetic Factors in Cancer: A Systematic Review and Meta-analysis
A partir d'une revue systématique de la littérature publiée entre mai 1990 et juillet 2011, cette méta-analyse évalue l'association entre des polymorphismes de VEGF et la réponse à un traitement anti-angiogénique
Angiogenesis is an important host process that interacts with cancer cells to promote growth, invasion and metastasis. Numerous therapeutic agents targeting the vascular endothelial growth factor (VEGF) pathway have been developed. Host variability in VEGF pathway can influence angiogenesis-dependent signalling, altering sensitivity to anti-angiogenic drugs and prognosis. A systematic review and meta-analysis was conducted (May 1990 - July 2011). Eligible studies involved cancer patients and compared polymorphisms in the VEGF pathway (VEGF and molecules directly interacting with VEGF: KDR, FLT1, FGF, FGF2, FGFR, NRP1, Endostatin (encoded by COL18A1) and reported one of the following outcomes: overall survival, progression-free survival, time-to-recurrence, disease-free survival, response rate or drug toxicity. We identified 48 cancer studies assessing prognosis and 12 cancer studies exploring pharmacogenetics of anti-VEGF therapy across various VEGF pathway polymorphisms. There was marked inter- and intra-disease site heterogeneity in the effect of polymorphisms on both outcome and response to therapy. Meta-analyses of five VEGF polymorphisms (+936CT, -460TC, +405GC, -1154GA and -2578CA) identified a significant prognostic relationship: VEGF +405GC variants demonstrated a highly statistically significant improvement in OS (HR=0.74, 95% CI = 0.60-0.91, P = 0.004). Variants (heterozygotes and/or homozygotes) of VEGF +405GC were significantly associated with improved survival in a meta-analysis of multiple cancer sites.
Clinical Cancer Research , résumé, 2012