Vascular endothelial growth factor polymorphisms and esophageal cancer prognosis.
OBJECTIVE
Vascular endothelial growth factor (VEGF) promotes angiogenesis and vascular permeability. The VEGF gene is polymorphic. We investigated the prognostic significance of three VEGF single nucleotide polymorphisms (SNP) in esophageal cancer.


METHODS
Three hundred sixty-one patients were genotyped for three VEGF SNPs (-460T/C, 405G/C, and 936C/T) using DNA extracted from prospectively collected blood samples. The association of each individual SNP, and haplotypes of the three SNPs, on overall survival (OS) was investigated.


RESULTS
The variant allele of 936C/T was associated with improved OS compared with the wild-type genotype (log-rank P < 0.001). This association remained significant for OS after adjustments for age, gender, performance status, and disease stage [VEGF 936C/T: adjusted hazard ratio (AHR), 0.70; 95% confidence interval (95% CI), 0.49-0.99; P = 0.04; VEGF 936T/T: AHR, 0.11; 95% CI, 0.02-0.82; P = 0.03]. No independent associations were found for VEGF -460T/C and VEGF 405G/C. The CGC haplotype of the three VEGF SNPs (-460T/C, 405G/C, and 936C/T) combined was associated with reduced OS compared with all other patients (CGC/CGC: AHR, 1.51; 95% CI, 1.00-2.30; P = 0.05).


CONCLUSIONS
VEGF 936C/T, and a haplotype of 460T/C, 405G/C, and 936C/T combined, has potential prognostic significance in esophageal cancer.
Bradbury
Penelope A
PA
Medical Oncology and Haematology, Department of Medicine, Princess Margaret Hospital, Ontario Cancer Institute, University of Toronto,Toronto, Ontario M5G 2M9, Canada.
Zhai
Rihong
R
Ma
Clement
C
Xu
Wei
W
Hopkins
Jessica
J
Kulke
Matthew J
MJ
Asomaning
Kofi
K
Wang
Zhaoxi
Z
Su
Li
L
Heist
Rebecca S
RS
Lynch
Thomas J
TJ
Wain
John C
JC
Christiani
David
D
Liu
Geoffrey
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D055815:Young Adult
D042461:Vascular Endothelial Growth Factor A