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VEGF −460T → C polymorphism and its association with VEGF expression and outcome to FOLFOX-4 treatment in patients with colorectal carcinoma

The Pharmacogenomics Journal volume 11, pages 227–236 (2011)Cite this article

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Abstract

The −460T → C polymorphism of vascular endothelial growth factor (VEGF) gene significantly increases its promoter activity. A pilot study was conducted to assess the influence of this polymorphism on clinicopathological features of patients with colorectal carcinoma. In total, 228 patients were enrolled, including 100 with stage II/III colorectal carcinoma receiving curative surgery and 128 with metastatic disease. An excellent correlation in VEGF −460 genotypes based on white blood cells and tumor tissues existed, but there was no between-group difference in patients with or without colorectal carcinoma. A marked increase in intratumor and circulating VEGF levels were observed in patients with the T/C or C/C genotypes (P<0.01), which was associated with increased extent of invasion, nodal involvement, poor histological differentiation, subsequent metastasis and shorter survival in stage II/III patients treated with curative surgery (P<0.01). For patients with metastatic disease, this polymorphism was associated with a lower response rate to FOLFOX-4 (P=0.03) and shorter survival (P<0.001). By multivariate analysis, this polymorphism was identified as an independent prognostic factor (P=0.01). These data suggest that −460T → C polymorphism of VEGF gene, by increasing VEGF expression and subsequent angiogenesis, could be a key determinant for increased tumor recurrence and a poor prognosis of patients with colorectal carcinoma. However, this study is exploratory and is not adjusted for multiple comparisons, requiring independent replication.

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Acknowledgements

This study was supported by a grant from The National Yang-Ming University Hospital (grant no. RD2008-002) to Wang Wei-Shu.

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Authors and Affiliations

  1. National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China

    M-H Chen, C-H Tzeng, P-M Chen, J-K Lin, T-C Lin, W-S Chen, J-K Jiang, H-S Wang & W-S Wang

  2. Division of Oncology and Hematology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China

    M-H Chen, C-H Tzeng & P-M Chen

  3. Division of Colorectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China

    J-K Lin, T-C Lin, W-S Chen, J-K Jiang & H-S Wang

  4. Department of Medicine, National Yang-Ming University Hospital, Yilan, Taiwan, Republic of China

    W-S Wang

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Chen, MH., Tzeng, CH., Chen, PM. et al. VEGF −460T → C polymorphism and its association with VEGF expression and outcome to FOLFOX-4 treatment in patients with colorectal carcinoma. Pharmacogenomics J 11, 227–236 (2011). https://doi.org/10.1038/tpj.2010.48

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