TY - JOUR
T1 - Vascular endothelial growth factor pathway polymorphisms as prognostic and pharmacogenetic factors in cancer
T2 - A systematic review and meta-analysis
AU - Eng, Lawson
AU - Azad, Abul Kalam
AU - Habbous, Steven
AU - Pang, Vincent
AU - Xu, Wei
AU - Maitland-van Der Zee, Anke H.
AU - Savas, Sevtap
AU - Mackay, Helen J.
AU - Amir, Eitan
AU - Liu, Geoffrey
PY - 2012/9/1
Y1 - 2012/9/1
N2 - Angiogenesis is an important host process that interacts with cancer cells to promote growth, invasion, and metastasis. Numerous therapeutic agents targeting the VEGF pathway have been developed. Host variability in VEGF pathway can influence angiogenesis-dependent signaling, altering sensitivity to antiangiogenic 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 intradisease site heterogeneity in the effect of polymorphisms on both outcome and response to therapy. Meta-analyses of 5 VEGF polymorphisms (+936C>T, -460T>C, +405G>C, -1154G>A, and -2578C>A) identified a significant prognostic relationship: VEGF +405G>C variants showed a highly statistically significant improvement in overall survival [HR, 0.74; 95% confidence interval, 0.60-0.91; P = 0.004]. Variants (heterozygotes and/or homozygotes) of VEGF +405G>C were significantly associated with improved survival in a meta-analysis of multiple cancer sites.
AB - Angiogenesis is an important host process that interacts with cancer cells to promote growth, invasion, and metastasis. Numerous therapeutic agents targeting the VEGF pathway have been developed. Host variability in VEGF pathway can influence angiogenesis-dependent signaling, altering sensitivity to antiangiogenic 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 intradisease site heterogeneity in the effect of polymorphisms on both outcome and response to therapy. Meta-analyses of 5 VEGF polymorphisms (+936C>T, -460T>C, +405G>C, -1154G>A, and -2578C>A) identified a significant prognostic relationship: VEGF +405G>C variants showed a highly statistically significant improvement in overall survival [HR, 0.74; 95% confidence interval, 0.60-0.91; P = 0.004]. Variants (heterozygotes and/or homozygotes) of VEGF +405G>C were significantly associated with improved survival in a meta-analysis of multiple cancer sites.
UR - http://www.scopus.com/inward/record.url?scp=84865761089&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865761089&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-12-1315
DO - 10.1158/1078-0432.CCR-12-1315
M3 - Review article
C2 - 22733538
AN - SCOPUS:84865761089
SN - 1078-0432
VL - 18
SP - 4526
EP - 4537
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 17
ER -
