The Importance of -460 C/T and +405 G/C Single Nucleotide Polymorphisms to the Function of Vascular Endothelial Growth Factor A in Colorectal Cancer

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2009 Nov 12

PMID 19904558

Citations 9

Authors

Torben F Hansen

Karen-Lise G Spindler

Karen A Lorentzen

Dorte A Olsen

Rikke F Andersen

Jan Lindebjerg

Ivan Brandslund

Anders Jakobsen

Affiliations

Soon will be listed here.

Abstract

Purpose: The present study investigated the functional influence of the single nucleotide polymorphisms (SNPs) -460 C/T and +405 G/C at vascular endothelial growth factor A (VEGF-A), mRNA and protein levels in colorectal cancer (CRC) and normal colorectal tissue.

Methods: Blood and tissue were collected from 113 patients surgically resected for colorectal cancer. SNPs were analysed from genomic DNA by PCR, the VEGF-A gene expression analysis was performed by RT-PCR and protein analysis by ELISA.

Results: The T-allele in the -460 C/T SNP and the C-allele in the +405 G/C SNP were associated with significantly lower VEGF-A protein levels in normal colorectal tissue. There were no differences in protein levels in the malignant tissue according to genotypes. No differences were observed at the gene expression levels either.

Conclusion: The results indicate that the two SNPs have a functional influence on the VEGF-A protein levels in normal colorectal tissue. The possible clinical implications of the findings need further investigation.

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References

Kumar H, Heer K, Lee P, Duthie G, Macdonald A, Greenman J . Preoperative serum vascular endothelial growth factor can predict stage in colorectal cancer. Clin Cancer Res. 1998; 4(5):1279-85. View

Kim K, Li B, Winer J, Armanini M, Gillett N, PHILLIPS H . Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature. 1993; 362(6423):841-4. DOI: 10.1038/362841a0. View

Renner W, Kotschan S, Hoffmann C, Obermayer-Pietsch B, Pilger E . A common 936 C/T mutation in the gene for vascular endothelial growth factor is associated with vascular endothelial growth factor plasma levels. J Vasc Res. 2001; 37(6):443-8. DOI: 10.1159/000054076. View

Garcia-Closas M, Malats N, Real F, Yeager M, Welch R, Silverman D . Large-scale evaluation of candidate genes identifies associations between VEGF polymorphisms and bladder cancer risk. PLoS Genet. 2007; 3(2):e29. PMC: 1802828. DOI: 10.1371/journal.pgen.0030029. View

Kuramochi H, Hayashi K, Uchida K, Miyakura S, Shimizu D, Vallbohmer D . Vascular endothelial growth factor messenger RNA expression level is preserved in liver metastases compared with corresponding primary colorectal cancer. Clin Cancer Res. 2006; 12(1):29-33. DOI: 10.1158/1078-0432.CCR-05-1275. View

Tokunaga T, Oshika Y, Abe Y, Ozeki Y, Sadahiro S, Kijima H . Vascular endothelial growth factor (VEGF) mRNA isoform expression pattern is correlated with liver metastasis and poor prognosis in colon cancer. Br J Cancer. 1998; 77(6):998-1002. PMC: 2150098. DOI: 10.1038/bjc.1998.164. View

Parkin D, Bray F, Ferlay J, Pisani P . Global cancer statistics, 2002. CA Cancer J Clin. 2005; 55(2):74-108. DOI: 10.3322/canjclin.55.2.74. View

Hofmann G, Langsenlehner U, Renner W, Langsenlehner T, Yazdani-Biuki B, Clar H . Common single nucleotide polymorphisms in the vascular endothelial growth factor gene and colorectal cancer risk. J Cancer Res Clin Oncol. 2007; 134(5):591-5. DOI: 10.1007/s00432-007-0322-x. View

Spindler K, Lindebjerg J, Nielsen J, Olsen D, Bisgard C, Brandslund I . Epidermal growth factor receptor analyses in colorectal cancer: a comparison of methods. Int J Oncol. 2006; 29(5):1159-65. View

10.

Schneider S, Park D, Yang D, El-Khoueiry A, Sherrod A, Groshen S . Gene expression in tumor-adjacent normal tissue is associated with recurrence in patients with rectal cancer treated with adjuvant chemoradiation. Pharmacogenet Genomics. 2006; 16(8):555-63. DOI: 10.1097/01.fpc.0000220563.44724.6d. View

11.

Andre T, Kotelevets L, Vaillant J, Coudray A, Weber L, Prevot S . Vegf, Vegf-B, Vegf-C and their receptors KDR, FLT-1 and FLT-4 during the neoplastic progression of human colonic mucosa. Int J Cancer. 2000; 86(2):174-81. DOI: 10.1002/(sici)1097-0215(20000415)86:2<174::aid-ijc5>3.0.co;2-e. View

12.

Holt R, Ralph S, Webb N, Watson C, Clark A, Mathieson P . Steroid-sensitive nephrotic syndrome and vascular endothelial growth factor gene polymorphisms. Eur J Immunogenet. 2003; 30(1):1-3. DOI: 10.1046/j.1365-2370.2003.00360.x. View

13.

Ku K, Wan L, Peng H, Tsai M, Tsai C, Tsai F . Vascular endothelial growth factor gene-460 C/T polymorphism is a biomarker for oral cancer. Oral Oncol. 2005; 41(5):497-502. DOI: 10.1016/j.oraloncology.2004.12.009. View

14.

Koukourakis M, Papazoglou D, Giatromanolaki A, Bougioukas G, Maltezos E, Sivridis E . VEGF gene sequence variation defines VEGF gene expression status and angiogenic activity in non-small cell lung cancer. Lung Cancer. 2004; 46(3):293-8. DOI: 10.1016/j.lungcan.2004.04.037. View

15.

George M, Tutton M, Janssen F, Arnaout A, Abulafi A, Eccles S . VEGF-A, VEGF-C, and VEGF-D in colorectal cancer progression. Neoplasia. 2001; 3(5):420-7. PMC: 1506210. DOI: 10.1038/sj.neo.7900186. View

16.

Takahashi H, Shibuya M . The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions. Clin Sci (Lond). 2005; 109(3):227-41. DOI: 10.1042/CS20040370. View

17.

Broll R, Erdmann H, Duchrow M, Oevermann E, Schwandner O, Markert U . Vascular endothelial growth factor (VEGF)--a valuable serum tumour marker in patients with colorectal cancer?. Eur J Surg Oncol. 2001; 27(1):37-42. DOI: 10.1053/ejso.2000.1052. View

18.

Houck K, Leung D, Rowland A, Winer J, Ferrara N . Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. J Biol Chem. 1992; 267(36):26031-7. View

19.

Howell W, Bateman A, Turner S, Collins A, Theaker J . Influence of vascular endothelial growth factor single nucleotide polymorphisms on tumour development in cutaneous malignant melanoma. Genes Immun. 2002; 3(4):229-32. DOI: 10.1038/sj.gene.6363851. View

20.

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W . Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004; 350(23):2335-42. DOI: 10.1056/NEJMoa032691. View