VEGF gene polymorphisms and susceptibility to colorectal cancer disease in Italian population.
BACKGROUND
The vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen involved in the process of angiogenesis, a crucial phase in tumor growth and metastasis. We carried out a case-control study to evaluate whether polymorphisms of VEGF gene modulate the risk of developing colorectal cancer disease (CCD).


METHODS
We evaluated VEGF -2578A/C, -460T/C, and +405C/G genotypes obtained from a series of 302 CCD patients and 115 controls from the Italian population using polymerase chain reaction restriction fragment length polymorphism assay.


RESULTS
Strong linkage disequilibrium (LD) was detected between -2578A/C and -460T/C (D' = 0.97; CI = 0.93-1) and between -2578A/C and +405C/G (D' = 0.97; CI = 0.98-1) in the case group. Complete LD was detected between -2578A/C and +405C/G and between -460T/C and +405C/G (D' = 1; CI = 0.84-1; CI = 0.82-1, respectively) in the control group. A reduced risk for the disease was associated with -2578C/A and -2578C/C (odds ratio (OR) = 0.34, CI = 0.162-0.676 and OR = 0.38, CI = 0.181-0.775, respectively). A direct association was found for carriers of the VEGF -460C/C polymorphism (OR = 3.55; CI = 1.659-8.469). We identified a protective haplotype -2578A, -460T, and +405G (OR = 0.04; CI = 0.009-0.19) and two different high-risk haplotypes -2578A, -460C, and +405G (OR = 1.90; CI = 1.31-2.27) and -2578C, -460C, and +405C (OR = 9.62; CI = 1.3-70.87).


CONCLUSIONS
The present study suggests that the VEGF gene polymorphisms may play a role in the development of colorectal cancer.
Maltese
Paolo
P
Department of Biomolecular Sciences, University of Urbino, Via Saffi, 2-61029, Urbino, Italy. paolo.maltese@uniurb.it
Canestrari
Emanuele
E
Ruzzo
Annamaria
A
Graziano
Francesco
F
Falcone
Alfredo
A
Loupakis
Fotios
F
Tonini
Giuseppe
G
Santini
Daniele
D
Magnani
Mauro
M
D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D044465:White People / Q000235:genetics*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A