Vascular Endothelial Growth Factor Pathway Polymorphisms as Prognostic and Pharmacogenetic Factors in Cancer: A Systematic Review and Meta-analysis

被引：44

作者：

Eng, Lawson ^{[1
,2
]}

Azad, Abul Kalam ^{[1
]}

Habbous, Steven ^{[1
]}

Pang, Vincent ^{[1
]}

Xu, Wei ^{[1
,2
]}

Maitland-van der Zee, Anke H. ^{[5
]}

Savas, Sevtap ^{[4
]}

Mackay, Helen J. ^{[2
]}

Amir, Eitan ^{[2
]}

Liu, Geoffrey ^{[1
,2
,3
]}

机构：

[1] Univ Hlth Network, Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada

[2] Univ Hlth Network, Princess Margaret Hosp, Dept Med, Div Med Oncol & Hematol, Toronto, ON M5G 2M9, Canada

[3] Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON, Canada

[4] Mem Univ Newfoundland, Discipline Genet, St John, NF, Canada

[5] Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, UIPS, Fac Sci, Utrecht, Netherlands

来源：

CLINICAL CANCER RESEARCH | 2012年 / 18卷 / 17期

关键词：

FACTOR GENE POLYMORPHISMS; SINGLE-NUCLEOTIDE POLYMORPHISMS; PREDICT TUMOR RECURRENCE; FACTOR VEGF GENE; BREAST-CANCER; PLUS BEVACIZUMAB; PROTEIN-LEVELS; SERUM VEGF; SURVIVAL; ASSOCIATION;

D O I：

10.1158/1078-0432.CCR-12-1315

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 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 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. Clin Cancer Res; 18(17); 4526-37. (C) 2012 AACR.

引用

页码：4526 / 4537

页数：12

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