Vascular endothelial growth factor 1498C/T, 936C/T polymorphisms associated with increased risk of colorectal adenoma: a Chinese case–control study
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Single nucleotide polymorphisms in vascular endothelial growth factor gene VEGF, 1498C/T and 936 C/T are associated with colorectal cancer. We sought to determine whether such genetic variability in VEGF contributes to susceptibility of colorectal adenoma (CRA), a presumably precancerous state of colorectal cancer. In this research, two aforementioned polymorphisms were investigated for CRA susceptibility in a Chinese case–control study. The epidemiological risk factors were collected through questionnaire. The plasma VEGF levels were measured via enzyme-linked immunosorbent assay (ELISA). The Taqman-Probe assay was used to determine genotypes in 224 CRA patients and 200 CRA-free controls. The clinicopathological data of each sample were collected for further correlation analysis. According to data analysis males, cigarette smokers, patients who carry metabolic syndrome or familial antecedent of adenomas were significantly associated with CRA risk. Plasma VEGF levels of CRA patients were higher than those of controls (P = 0.003). This difference is independent of genotypes. The carriers with 936CT and CT+TT had higher risk of CRA in comparison with controls (CT vs. CC, OR 2.00, 95% CI 1.23–3.25, P = 0.006; CT+TT vs. CC, OR 2.04, 95% CI 1.28–3.26, P = 0.003). 936-T allele was associated with increased risk of CRA (OR 1.91, 95% CI 1.25–2.91, P = 0.003). Both CRA and control show no difference in the genotype of 1498C/T and the allele frequency of C−/T−. CRA patients with haplotype 1498T+936T presented significantly higher risk than those with wild-type 1498T+936C. Moreover, patients carrying 936CT+TT and 936-T allele demonstrated a tendency for villous adenoma. CRA patients have elevated plasma VEGF levels. The VEGF 936C/T polymorphism and 1498T+936T haplotype were found to be associated with increased CRA susceptibility.
KeywordsColorectal adenoma Vascular endothelial growth factor Polymorphism SNP Chinese
Vascular endothelial growth factor
Single nucleotide polymorphism
Body mass index
This work was financially supported by the Hubei Key Scientific and Technological Project of Eleventh Five-Year Plan (2006AA301A05); grants from the National Natural Science Foundation of China (30901356), new college teacher grants from the Ministry of Education of China (20090141120014) and Youth teacher grants from Wuhan University (3082008). We thank the nurses from Zhongnan and Renmin Hospital for their constant and generous support to this study. The critical instruments in this report were supported by School of Basic Medical Science, Wuhan University.
Conflict of interest
- 4.Townsend CM, Beauchamp RD, Evers BM, Mattox KL (2007) Sabiston text book of surgery: the biological basis of modern surgical practice, 18th edn. W.B. Saunders Company, PhiladelphiaGoogle Scholar
- 22.Chae YS, Kim JG, Sohn SK, Cho YY, Ahn BM, Moon JH, Jeon SW, Park JY, Lee IT, Jun SH, Choi GS (2008) Association of vascular endothelial growth factor gene polymorphisms with susceptibility and clinicopathologic characteristics of colorectal cancer. J Korean Med Sci 23:421–427PubMedCrossRefGoogle Scholar
- 23.Hofmann G, Langsenlehner U, Renner W, Langsenlehner T, Yazdani-Biuki B, Clar H, Gerger A, Wehrschuetz M, Samonigg H, Krippl P (2008) Common single nucleotide polymorphisms in the vascular endothelial growth factor gene and colorectal cancer risk. J Cancer Res Clin Oncol 134:591–595PubMedCrossRefGoogle Scholar
- 26.Hamilton SR, Aaltonen LA (2000) Tumours of the digestive system: pathology & genetics. WHO classification. IARC Press, LyonGoogle Scholar
- 27.Van den Donk M, Buijsse B, Van den Berg SW, Ocké MC, Harryvan JL, Nagengast FM, Kok FJ, Kampman E (2005) Dietary intake of folate and riboflavin, MTHFR C677T genotype, and colorectal adenoma risk: a Dutch case–control study. Cancer Epidemiol Biomarkers Prev 14(6):1562–1566PubMedCrossRefGoogle Scholar
- 42.Garrow D, Delegge M (2008) Metabolic syndrome is a risk factor for colorectal cancer in the United States. Am J Gastroenterol 103:S545–S546Google Scholar
- 43.Little J, Higgins JP, Ioannidis JP, Moher D, Gagnon F, von Elm E, Khoury MJ, Cohen B, Davey-Smith G, Grimshaw J, Scheet P, Gwinn M, Williamson RE (2009) Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE statement. Ann Intern Med 150(3):206–215PubMedGoogle Scholar