Vascular endothelial growth factor polymorphisms in gastric cancer development, prognosis, and survival.
BACKGROUND
Angiogenesis plays an important role in growth, progression, and metastasis of tumors. Vascular endothelial growth factor (VEGF) overexpression has been associated with advanced stage and poor survival in several cancers.


METHODS
The association of functional single nucleotide polymorphisms (SNPs) of VEGF gene with gastric cancer development, prognosis, and survival in a case-control study of 100 gastric cancer Greek patients was evaluated. The genotyping was performed by PCR-RFLP analysis.


RESULTS
Our results revealed a marginally significant association of the 634CC genotype (P = 0.042) with increased risk for gastric cancer development. None of the rest of the examined polymorphisms or haplotypes conferred any gastric cancer susceptibility. A strong association between the -2578AA (P = 0.025), -634CC (P = 0.013), +936CT (P = 0.028), +936TT (P = 0.0001) genotypes and a larger tumor size was observed, while the 2578AA and -634CC genotypes were strongly correlated to poor differentiation (P = 0.01) and advanced stage of disease (P = 0.039), respectively. In addition, our results indicated that metastatic disease frequency was more accentuated among the +936TT carriers (P = 0.0035). Interestingly, carrying the -634CC genotype was associated with decreased overall survival rates (46.67%).


CONCLUSIONS
The present study suggests that VEGF polymorphisms may contribute to gastric tumor characteristics; these observations, however, requiring further confirmation in a larger multi-ethnic study.
Tzanakis
Nikolaos
N
4th Surgical Department, Attikon Hospital, University of Athens, Athens, Greece.
Gazouli
Maria
M
Rallis
George
G
Giannopoulos
George
G
Papaconstantinou
Ioannis
I
Theodoropoulos
George
G
Pikoulis
Emmanouil
E
Tsigris
Christos
C
Karakitsos
Petros
P
Peros
George
G
Nikiteas
Nikolaos
N
D000368:Aged; D016022:Case-Control Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D013274:Stomach Neoplasms / Q000098:blood supply / Q000209:etiology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A