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Association of single nucleotide polymorphisms in vascular endothelial growth factor gene with bladder cancer risk

Medical Oncology volume 30, Article number: 509 (2013) Cite this article

Abstract

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific potent mitogen involved in a number of pathologic processes, including angiogenesis, tumor growth, and metastasis. Polymorphisms of VEGF gene have been associated with susceptibility to several cancers. VEGF gene susceptibility to bladder cancer (BC), however, still remains controversial. We analyzed association of the -2578C/A, -7C/T, -2549I/D, and -1001G/C polymorphism of the VEGF gene with bladder cancer (BC) risk and interaction of these polymorphisms with lifestyle and demographic factors. We genotyped -2578C/A, -7C/T, -2549I/D and -1001G/C by PCR–restriction fragment length polymorphism and amplification refractory mutation specific method to evaluate risk in 200 BC patients and 250 healthy controls from North Indian population. Significant association for BC risk in heterozygous CA genotype (1.69-fold) in VEGF-2578C/A and heterozygous genotype of VEGF-1001G/C (p = 0.032) was observed. Interestingly, VEGF-2549I/D genotype showed reduced risk for BC. The gene–gene combination analysis revealed DD-GG with reduced risk (p = 0.018) of VEGF-2549I/D and VEGF-1001G/C, and combination CA-GG of VEGF-2578C/A and VEGF-1001G/C demonstrated 1.75-fold risk for BC. Our findings suggested that polymorphism -2578C/A and -1001G/C in the promoter of VEGF gene may play a significant role in mediating the bladder cancer risk, whereas VEGF-2549I/D genotype appears to be protective for BC.

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References

  1. Sinha R, Anderson DE, McDonald SS, et al. Cancer risk and diet in India. J Postgrad Med. 2003;49:222–8.

    PubMed  CAS  Google Scholar 

  2. Ferrara N. Vascular endothelial growth factors as a target for anticancer therapy. Oncologist. 2004;9:2–10.

    PubMed  Article  CAS  Google Scholar 

  3. Kaiser PK. Antivascular endothelial growth factor agents and their development: therapeutic implications in ocular diseases. Am J Ophthalmol. 2006;142:660–8.

    PubMed  Article  CAS  Google Scholar 

  4. Watson CJ, Webb NJ, Bottomley MJ, et al. Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production. Cytokine. 2000;12:1232–5.

    PubMed  Article  CAS  Google Scholar 

  5. Goebel S, Huang M, Davis WC, et al. VEGF-A stimulation of leukocyte adhesion to colonic microvascular endothelium: implications for inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol. 2006;290:G648–54.

    PubMed  Article  CAS  Google Scholar 

  6. Wang Y, Chang J, Li YC, et al. Shear stress and VEGF activate IKK via the Flk-1/Cbl/Akt signaling pathway. Am J Physiol Heart Circ Physiol. 2004;286:H685–92.

    PubMed  Article  CAS  Google Scholar 

  7. Yang B, Cross DF, Ollerenshaw M, et al. Polymorphisms of the vascular endothelial growth factor and susceptibility to diabetic microvascular complications in patients with type 1 diabetes mellitus. J Diabetes Complicat. 2003;17:1–6.

    PubMed  Article  Google Scholar 

  8. Colombel M, Soloway M, Akaza H. Epidemiology, staging, grading, and risk stratification of bladder cancer. Eur Urol Suppl. 2008;7:618–26.

    Article  Google Scholar 

  9. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.

    PubMed  Article  CAS  Google Scholar 

  10. Bazzaz TJ, Amoli MM, Pravica V, et al. VEGF gene polymorphism association with diabetic neuropathy. Mol Biol Rep. 2010;37:3625–30.

    Article  Google Scholar 

  11. Aggarwal S, Parveen F, Faridi RM, et al. Vascular endothelial growth factor gene polymorphisms in North Indian patients with recurrent miscarriages. Reprod Biomed Online. 2011;22:59–64.

    PubMed  Article  CAS  Google Scholar 

  12. Kawai Y, Sakano S, Korenaga Y, et al. Associations of single nucleotide polymorphisms in the vascular endothelial growth factor gene with the characteristics and prognosis of renal cell carcinomas. Eur Urol. 2007;52:1147–55.

    PubMed  Article  CAS  Google Scholar 

  13. Jacobsen J, Rasmuson T, Grankvist K, et al. Vascular endothelial growth factor as prognostic factor in renal cell carcinoma. J Urol. 2000;163:343–7.

    PubMed  Article  CAS  Google Scholar 

  14. Wang T, Hu K, Ren J, et al. Polymorphism of VEGF-2578C/A associated with the risk and aggressiveness of nasopharyngeal carcinoma in a Chinese population. Mol Biol Rep. 2010;37:59–65.

    PubMed  Article  CAS  Google Scholar 

  15. Zhao ZZ, Nyholt DR, Thomas S, et al. Polymorphisms in the vascular endothelial growth factor gene and the risk of familial endometriosis. Mol Hum Reprod. 2008;14:531–8.

    PubMed  Article  CAS  Google Scholar 

  16. Mittal RD, Srivastava P, Singh V, et al. Association of common variants of vascular endothelial growth factor and interleukin-18 genes with allograft survival in renal transplant recipients of North India. DNA Cell Biol. 2011;30:309–15.

    PubMed  Article  CAS  Google Scholar 

  17. Prakash S, Prasad N, Sharma RK, et al. Vascular endothelial growth factor gene polymorphisms in North Indian patients with end stage renal disease. Cytokine. 2012;58:261–6.

    PubMed  Article  CAS  Google Scholar 

  18. Zhang L, Zhang G, Wang P, et al. Association of vascular endothelial growth factor -2578C/A gene polymorphism in Chinese patients with colon cancer. Genet Test Mol Biomarkers. 2011;15:117–21.

    PubMed  Article  CAS  Google Scholar 

  19. Pander J, Gelderblom H, Guchelaar HJ. Pharmacogenetics of EGFR and VEGF inhibition. Drug Discov Today. 2007;12:1054–60.

    PubMed  Article  CAS  Google Scholar 

  20. Buraczynska M, Ksiazek P, Baranowicz-Gaszczyk I, et al. Association of the VEGF gene polymorphism with diabetic retinopathy in type 2 diabetes patients. Nephrol Dial Transplant. 2007;22:827–32.

    PubMed  Article  CAS  Google Scholar 

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Acknowledgments

This study was funded by Department of Science & Technology (DST), New Delhi. The assistance of relevant clinical information of the patients by the Urologists and Pathologist is duly acknowledged. P. K. J. is thankful for UGC-JRF from University Grant Commission, New Delhi.

Conflict of interest

All authors declare no conflicts of interest to this work.

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Affiliations

  1. Department of Urology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, India

    Praveen Kumar Jaiswal & Rama Devi Mittal

  2. Department of Biotechnology, Awadhesh Pratap Singh University, Rewa, 486003, India

    Nidhi Tripathi & Alka Shukla

Authors
  1. Praveen Kumar Jaiswal
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  2. Nidhi Tripathi
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  3. Alka Shukla
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  4. Rama Devi Mittal
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Corresponding author

Correspondence to Rama Devi Mittal.

Additional information

Nidhi Tripathi and Alka Shukla have equally contributed to this work.

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Jaiswal, P.K., Tripathi, N., Shukla, A. et al. Association of single nucleotide polymorphisms in vascular endothelial growth factor gene with bladder cancer risk. Med Oncol 30, 509 (2013). https://doi.org/10.1007/s12032-013-0509-8

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  • DOI: https://doi.org/10.1007/s12032-013-0509-8

Keywords

  • Bladder cancer
  • VEGF gene polymorphism
  • RFLP
  • BCG immunotherapy
  • Haplotypes