VEGF gene polymorphisms and susceptibility to colorectal cancer disease in Italian population

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). 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. Strong linkage disequilibrium (LD) was detected between -2578A/C and -460T/C (D'aEuro parts per thousand= 0.97; CI = 0.93-1) and between -2578A/C and +405C/G (D'aEuro parts per thousand= 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'aEuro parts per thousand= 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). The present study suggests that the VEGF gene polymorphisms may play a role in the development of colorectal cancer.