Skip to main content

Advertisement

SpringerLink
Log in

Prognostic significance of vascular endothelial growth factor gene polymorphisms in patients with colorectal cancer

  • Original Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

Angiogenesis plays an important role in tumor development, progression, and metastasis. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. However, the contribution of common VEGF polymorphisms to colorectal cancer (CRC) prognosis remains unclear.

Methods

We have genotyped four polymorphisms of VEGF (−2578C>A, −1154G>A, −634G>C, and 936C>T) in 350 CRC cases from the Korean population. The genotyping of VEGF polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism assay.

Results

Although not every VEGF polymorphism was significantly correlated with patient prognosis in overall 350 CRC patients, we found that the VEGF −2578CA genotype was associated with a significantly poor prognosis for rectal cancers compared to the CC genotype (HR = 2.156; 95 % CI 1.090–4.267; P = 0.028). In addition, we found that the −2578A/−1154G/−634G/+936C haplotype was significantly associated with a decreased overall survival (OS) rate in all 350 CRC patients (HR = 2.530; 95 % CI 1.340–4.780; P = 0.004). In combination analysis, we found that the combined VEGF −2578CA+AA/−1154GG genotype was associated with a poor OS rate in all 350 CRC patients (HR = 2.068; 95 % CI 1.159–3.693; P = 0.015).

Conclusions

The VEGF gene polymorphisms investigated in this study were not found to be independent prognostic markers in Korean CRC populations. However, our results suggest that the VEGF −2578C>A variant may be a potential genetic marker for rectal cancer prognosis. Further large population studies are warranted to define whether the −2578C>A polymorphism is a prognostic marker of rectal cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364

    Article  CAS  PubMed  Google Scholar 

  2. Yancopoulos GD, Davis S, Gale NW et al (2000) Vascular-specific growth factors and blood vessel formation. Nature (Lond) 407:242–248

    Article  CAS  Google Scholar 

  3. Dvorak HF, Brown LF, Detmar M et al (1995) Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 146:1029–1039

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Cascinu S, Staccioli MP, Gasparini G et al (2000) Expression of vascular endothelial growth factor can predict event-free survival in stage II colon cancer. Clin Cancer Res 6:2803–2807

    CAS  PubMed  Google Scholar 

  5. Lee JC, Chow NH, Wang ST et al (2000) Prognostic value of vascular endothelial growth factor expression in colorectal cancer patients. Eur J Cancer 36:748–753

    Article  CAS  PubMed  Google Scholar 

  6. Fernando NH, Hurwitz HI (2004) Targeted therapy of colorectal cancer: clinical experience with bevacizumab. Oncologist 9(suppl 1):11–18

    Article  CAS  PubMed  Google Scholar 

  7. Brogan IJ, Khan N, Isaac K et al (1999) Novel polymorphisms in the promoter and 5′ UTR regions of the human vascular endothelial growth factor gene. Hum Immunol 60:1245–1249

    Article  CAS  PubMed  Google Scholar 

  8. Bae SJ, Kim JW, Kang H et al (2008) Gender-specific association between polymorphism of vascular endothelial growth factor (VEGF 936 C>T) gene and colon cancer in Korea. Anticancer Res 28:1271–1276

    CAS  PubMed  Google Scholar 

  9. Cao C, Fang JJ, Ying T et al (2010) Vascular endothelial growth factor +936C/T and +405G/C polymorphisms and cancer risk: a meta-analysis. Arch Med Res 41:548–557

    Article  CAS  PubMed  Google Scholar 

  10. Choi YS, Choi JK, Kim JW et al (2011) Association of the vascular endothelial growth factor (VEGF −1154G>A) polymorphism in patients with colorectal cancer. Genes Genom 33:133–138

    Article  CAS  Google Scholar 

  11. Dassoulas K, Gazouli M, Rizos S et al (2009) Common polymorphisms in the vascular endothelial growth factor gene and colorectal cancer development, prognosis, and survival. Mol Carcinog 48:563–569

    Article  CAS  PubMed  Google Scholar 

  12. Kim JG, Chae YS, Sohn SK et al (2008) Vascular endothelial growth factor gene polymorphisms associated with prognosis for patients with colorectal cancer. Clin Cancer Res 14:62–66

    Article  CAS  PubMed  Google Scholar 

  13. Hansen TF, Spindler KG, Andersen RF et al (2010) The prognostic value of haplotypes in the vascular endothelial growth factor A gene in colorectal cancer. Cancers 2:1405–1418

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Vidaurreta M, Sanchez-Munoz R, Veganzones S et al (2010) Vascular endothelial growth factor gene polymorphisms in patients with colorectal cancer. Rev Esp Enferm Dig 102:20–31

    CAS  PubMed  Google Scholar 

  15. The International HapMap Consortium (2003) The International HapMap Project. Nature 426:789–796

    Google Scholar 

  16. Del Bo R, Scarlato M, Ghezzi S et al (2005) Vascular endothelial growth factor gene variability is associated with increased risk for AD. Ann Neurol 57:373–380

    Article  PubMed  Google Scholar 

  17. Papazoglou D, Galazios G, Koukourakis MI et al (2004) Vascular endothelial growth factor gene polymorphisms and pre-eclampsia. Mol Hum Reprod 10:321–324

    Article  CAS  PubMed  Google Scholar 

  18. Kim EJ, Jeong P, Quan C et al (2005) Genotypes of TNF-alpha, VEGF, hOGG1, GSTM1, and GSTT1: useful determinants for clinical outcome of bladder cancer. Urology 65:70–75

    Article  PubMed  Google Scholar 

  19. Tzanakis N, Gazouli M, Rallis G et al (2006) Vascular endothelial growth factor polymorphisms in gastric cancer development, prognosis, and survival. J Surg Oncol 94:624–630

    Article  CAS  PubMed  Google Scholar 

  20. Heist RS, Zhai R, Liu G et al (2008) VEGF polymorphisms and survival in early-stage non-small-cell lung cancer. J Clin Oncol 26:856–862

    Article  CAS  PubMed  Google Scholar 

  21. Jin Q, Hemminki K, Enquist K et al (2005) Vascular endothelial growth factor polymorphisms in relation to breast cancer development and prognosis. Clin Cancer Res 11: 3647–3653

    Google Scholar 

  22. Lu H, Shu XO, Cui Y et al (2005) Association of genetic polymorphisms in the VEGF gene with breast cancer survival. Cancer Res 65:5015–5019

    Article  CAS  PubMed  Google Scholar 

  23. Awata T, Inoue K, Kurihara S et al (2002) A common polymorphism in the 5′-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes 51:1635–1639

    Article  CAS  PubMed  Google Scholar 

  24. Koukourakis MI, Papazoglou D, Giatromanolaki A et al (2004) VEGF gene sequence variation defines VEGF gene expression status and angiogenic activity in non-small cell lung cancer. Lung Cancer 46:293–298

    Article  PubMed  Google Scholar 

  25. Watson CJ, Webb NJ, Bottomley MJ (2000) Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production. Cytokine 12:1232–1235

    Article  CAS  PubMed  Google Scholar 

  26. Ungerbäck J, Elander N, Dimberg J et al (2009) Analysis of VEGF polymorphisms, tumor expression of VEGF mRNA and colorectal cancer susceptibility in a Swedish population. Mol Med Report 2:435–439

    Google Scholar 

  27. Des Guetz G, Uzzan B, Nicolas P et al (2006) Microvessel density and VEGF expression are prognostic factors in colorectal cancer. meta-analysis of the literature. Br J Cancer 94:1823–1832

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (2009-0075784 & 2012-007033).

Conflict of interest

The authors declare that they have no conflicts of interest for this study.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, School of Medicine, CHA University, Seongnam, South Korea

    Moon Ju Jang, So Young Chong & Doyeun Oh

  2. Department of Surgery, School of Medicine, CHA University, Seongnam, South Korea

    Jong Woo Kim

  3. Institute for Clinical Research, School of Medicine, CHA University, 351, Yatap-dong, Bundang-gu, Seongnam, 463-712, South Korea

    Young Joo Jeon, So Young Chong, Doyeun Oh & Nam Keun Kim

Authors
  1. Moon Ju Jang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jong Woo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Young Joo Jeon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. So Young Chong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Doyeun Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nam Keun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nam Keun Kim.

Additional information

M. J. Jang and J. W. Kim contributed equally to this work.

About this article

Cite this article

Jang, M.J., Kim, J.W., Jeon, Y.J. et al. Prognostic significance of vascular endothelial growth factor gene polymorphisms in patients with colorectal cancer. Int J Clin Oncol 18, 1032–1041 (2013). https://doi.org/10.1007/s10147-012-0493-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-012-0493-6

Keywords

Search

Navigation