Abstract
Vascular endothelial growth factor (VEGF) polymorphisms, specifically +405G/C (rs2010963), reportedly influence the risk for various digestive cancers. However, the consequences of these polymorphisms remain controversial and ambiguous. Therefore, we performed a meta-analysis of 11 studies with VEGF +405G/C genotyping on 2,862 patients and 3,028 controls using the random effects model. We obtained a pooled odds ratio (OR) of 1.04 (95 % confidence interval (CI) = 0.86–1.26) for the recessive genetic model, 1.07 (95 % CI = 0.81–1.42) for the dominant genetic model, 1.09 (95 % CI = 0.81–1.47) for the homozygote comparison, and 1.03 (95 % CI = 0.83–1.27) for the heterozygote comparison. In the subgroup analysis of the recessive model, the OR was 1.20 (95 % CI = 1.02–1.40) in colorectal cancer. These results show that VEGF +405G/C polymorphisms are unlikely to be a major determinant of susceptibility to digestive cancer. Furthermore, the subgroup analysis of recessive model indicates that VEGF +405G/C polymorphisms increase the risk for colorectal cancer.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ferrara N. Vascular endothelial growth factor as a target for anticancer therapy. Oncologist. 2004;9 Suppl 1:2–10.
Brogan IJ, Khan N, Isaac K, Hutchinson JA, Pravica V, Hutchinson IV. Novel polymorphisms in the promoter and 5′UTR regions of the human vascular endothelial growth factor gene. Hum Immunol. 1999;60:1245–9.
Chen P, Zhu J, Liu DY, Li HY, Xu N, Hou M. Over-expression of survivin and VEGF in small-cell lung cancer may predict the poorer prognosis. Med Oncol. 2014;31(1):775.
Hardenberg J, Martini T, Knauer A, Ströbel P, Becker A, Herrmann E, et al. Expression and predictive value of lymph-specific markers in urothelial carcinoma of the bladder. Urol Oncol. 2014;32(1):54. e9-54.e17.
Zhen W, Peng W, Xiaojun L. Association of the vascular endothelial growth factor (VEGF) gene single-nucleotide polymorphisms with osteosarcoma susceptibility in a Chinese population. Cancer Bio Mark. 2013;13(4):235–41.
Martinez-Fierro ML, Garza-Veloz I, Rojas-Martinez A. Positive association between vascular endothelial growth factor (VEGF) −2578C/A variant and prostate cancer. Cancer Bio Mark. 2013;13(4):235–41.
Guo-Qiang C, Jian-bin L, Guang-Zhi W, Jin-E D. Assessment of the associations between three VEGF polymorphisms and risk of prostate cancer. Tumor Biol. 2013. doi:10.1007/s13277-013-1250-9.
Dassoulas K, Gazouli M, Rizos S, Theodoropoulos G, Christoni Z, Nikiteas N, et al. Common polymorphisms in the vascular endothelial growth factor gene and colorectal cancer development, prognosis, and survival. Mol Carcinog. 2009;48:563–9.
Hofmann G, Langsenlehner U, Renner W, Langsenlehner T, Yazdani-Biuki B, Clar H, et al. Common single nucleotide polymorphisms in the vascular endothelial growth factor gene and colorectal cancer risk. J Cancer Res Clin Oncol. 2008;134:591–5.
Maltese P, Canestrari E, Ruzzo A, Graziano F, Falcone A, Loupakis F, et al. VEGF gene polymorphisms and susceptibility to colorectal cancer disease in Italian population. Int J Color Dis. 2009;24:165–70.
Chae YS, Kim JG, Sohn SK, Cho YY, Ahn BM, Moon JH, et al. Association of vascular endothelial growth factor gene polymorphisms with susceptibility and clinicopathologic characteristics of colorectal cancer. J Korean Med Sci. 2008;23:421–7.
Al-Moundhri MS, Al-Nabhani M, Burney IA, Al-Farsi A, Al-Bahrani B. Gastric cancer risk predisposition and prognostic significance of vascular endothelial growth factor (VEGF) gene polymorphisms—a case–control study in an Omani population. Mol Carcinog. 2009;48:1170–6.
Chae YS, Kim JG, Sohn SK, Cho YY, Moon JH, Bae HI, et al. Investigation of vascular endothelial growth factor gene polymorphisms and its association with clinicopathologic characteristics in gastric cancer. Oncology. 2006;71:266–72.
Guan X, Zhao H, Niu J, Tang D, Ajani JA, Wei Q. The VEGF −634G > C promoter polymorphism is associated with risk of gastric cancer. BMC Gastroenterol. 2009;9:77.
Tzanakis N, Gazouli M, Rallis G, Giannopoulos G, Papaconstantinou I, Theodoropoulos G, et al. Vascular endothelial growth factor polymorphisms in gastric cancer development, prognosis, and survival. J Surg Oncol. 2006;94:624–30.
Zhou Y, Li N, Zhuang W, Wu X. Vascular endothelial growth factor (VEGF) gene polymorphisms and gastric cancer risk in a Chinese Han population. Mol Carcinog. 2011;50:184–8.
Zhai R, Liu G, Asomaning K, Su L, Kulke MH, Heist RS, et al. Genetic polymorphisms of VEGF, interactions with cigarette smoking exposure and esophageal adenocarcinoma risk. Carcinogenesis. 2008;29:2330–4.
Kammerer PW, Toyoshima T, Eletr S, Kammerer P, Kuhr K, AI-Nawas B, et al. Single nucleotide polymorphisms of the vascular endothelial growth factor gene associated with incidence of oral squamous cell carcinoma. J Oral Pathol Med. 2010;39:786–92.
Kai H, Yong Z, Rensheng W. Current evidence on VEGF +405G/C polymorphism and malignancy susceptibility: a meta-analysis involving 30 studies. Twin Res Hum Gen et. 2012;15(4):496–502.
Li A, Gao P, Wang Z. Positive association of the vascular endothelial growth factor-A +405 GG genotype and poor survival in stage I-II gastric cancer in the northern Chinese population. Mol Biol Rep. 2013;40(3):2741–8.
Author information
Authors and Affiliations
Corresponding authors
Additional information
Qing Guo, Sheng-Bin Dai, and Feng Shen contributed equally to this work.
Rights and permissions
About this article
Cite this article
Guo, Q., Dai, SB., Shen, F. et al. VEGF +405G/C (rs2010963) polymorphisms and digestive system cancer risk: a meta-analysis. Tumor Biol. 35, 4977–4982 (2014). https://doi.org/10.1007/s13277-014-1655-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-014-1655-0