VEGF gene polymorphisms and susceptibility to colorectal cancer disease in Italian population |
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Authors: | Paolo Maltese Emanuele Canestrari Annamaria Ruzzo Francesco Graziano Alfredo Falcone Fotios Loupakis Giuseppe Tonini Daniele Santini Mauro Magnani |
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Affiliation: | (1) Department of Biomolecular Sciences, University of Urbino, Via Saffi, 2-61029 Urbino, Italy;(2) Medical Oncology, Hospital of Pesaro, Pesaro, Italy;(3) Medical Oncology, Hospital of Livorno, Livorno, Italy;(4) Medical Oncology, Campus Biomedico, Rome, Italy |
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Abstract: | 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). Materials and 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. Paolo Maltese and Emanuele Canestrari contributed equally to the study. |
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Keywords: | VEGF Polymorphism Colorectal Cancer SNP |
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