Skip to main content

Advertisement

Log in

Association of VEGF and VEGFR1 polymorphisms with breast cancer risk in North Indians

  • Research Article
  • Published:
Tumor Biology

Abstract

The aim of present study was to evaluate the relationship between vascular endothelial growth factor (VEGF) −2578C/A, −2549I/D, −460T/C and −7C/T and VEGFR1 −710C/T polymorphisms with risk to breast cancer in North Indians. A total of 204 sporadic breast cancer patients and 204 controls were recruited for this case-control study. Significantly increased frequency of II genotype of −2549I/D polymorphism was observed in patients as compared to control individuals (odds ratio (OR) = 2.76, 95 % confidence interval (CI), 1.55–4.92; p = 0.0005). VEGF −2578AA genotype (OR = 2.87; 95 % CI, 1.61–5.10; p = 0.0003) and A allele (OR = 1.65, 95 % CI, 1.25–2.18; p = 0.0004) were found to be associated with increased risk for breast cancer. Individuals carrying CC genotype (OR = 2.23, 95 % CI, 1.25–3.97) and C allele (OR = 1.42, 95 % CI, 1.07–1.87) of VEGF −460T/C polymorphism were at higher risk of breast cancer. There was no significant difference in genotype and allele distribution of VEGF −7C/T and VEGFR1 −710C/T polymorphisms between cases and control individuals (p > 0.05). Linkage disequilibrium analysis showed a strong linkage between VEGF −2549I/D and −2578C/A polymorphisms (Lewontin’s \( \overset{^{\prime }}{D} \) = 0.99; r 2 = 0.97), −2549I/D and −460T/C (\( \overset{^{\prime }}{D} \) = 0.94; r 2 = 0.84), and −2578C/A and −460T/C polymorphisms (\( \overset{^{\prime }}{D} \) = 0.93; r 2 = 0.83). In the present study, we concluded that VEGF −2549I/D, −2578C/A and −460T/C polymorphisms are associated with risk to breast cancer in Punjab, North India.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Abbreviations

VEGF :

Vascular endothelial growth factor

SNP:

Single-nucleotide polymorphism

UTR:

Untranslated region

HWE:

Hardy-Weinberg equilibrium

PCR:

Polymerase chain reaction

RFLP:

Restriction fragment length polymorphism

ARMS:

Amplification refractory mutation system

OR:

Odds ratio

CI:

Confidence interval

References

  1. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98(19):10869–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Schoppmann SF, Horvat R, Birner P. Lymphatic vessels and lymphangiogenesis in female cancer: mechanisms, clinical impact and possible implications for anti-lymphangiogenic therapies. Oncol Rep. 2002;9(3):455–60.

    PubMed  Google Scholar 

  3. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996;86(3):353–64.

    Article  CAS  PubMed  Google Scholar 

  4. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature. 2000;407(6801):249–57.

    Article  CAS  PubMed  Google Scholar 

  5. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    Article  CAS  PubMed  Google Scholar 

  6. Carmeliet P. Angiogenesis in health and disease. Nat Med. 2003;9(6):653–60.

    Article  CAS  PubMed  Google Scholar 

  7. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. J Nat Med. 2003;9(6):669–76.

    Article  CAS  Google Scholar 

  8. Alon T, Hemo I, Itin A, Pe’er J, Stone J, Keshet E. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med. 1995;1(10):1024–8.

    Article  CAS  PubMed  Google Scholar 

  9. Benjamin LE, Keshet E. Conditional switching of vascular endothelial growth factor (VEGF) expression in tumors: induction of endothelial cell shedding and regression of hemangioblastoma-like vessels by VEGF withdrawal. Proc Natl Acad Sci U S A. 1997;94(16):8761–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Vincenti V, Cassano C, Rocchi M, Persico G. Assignment of the vascular endothelial growth factor gene to human chromosome 6p21.3. Circulation. 1996;93(8):1493–5.

    Article  CAS  PubMed  Google Scholar 

  11. Brogan IJ, Khan N, Isaac K, Hutchinson JA, Pravica V, Hutchinson IV. Novel polymorphisms in the promoter and 5′ UTR regions of the human vascular endothelial growth factor gene. Hum Immunol. 1999;60(12):1245–9.

    Article  CAS  PubMed  Google Scholar 

  12. Watson CJ, Webb NJ, Bottomley MJ, Brenchley PE. Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production. Cytokine. 2000;12(8):1232–5.

    Article  CAS  PubMed  Google Scholar 

  13. Akiri G, Nahari D, Finkelstein Y, Le SY, Elroy-Stein O, Levi BZ. Regulation of vascular endothelial growth factor (VEGF) expression is mediated by internal initiation of translation and alternative initiation of transcription. Oncogene. 1998;17(2):227–36.

    Article  CAS  PubMed  Google Scholar 

  14. Huez I, Creancier L, Audigier S, Gensac MC, Prats AC, Prats H. Two independent internal ribosome entry sites are involved in translation initiation of vascular endothelial growth factor mRNA. Mol Cell Biol. 1998;18(11):6178–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. 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. 2000;37(6):443–8.

    Article  CAS  PubMed  Google Scholar 

  16. Awata T, Inoue K, Kurihara S, Ohkubo T, Watanabe M, Inukai K, et al. A common polymorphism in the 5′-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes. 2002;51(5):1635–9.

    Article  CAS  PubMed  Google Scholar 

  17. Mohammadi M, Ollier WE, Hutchinson IV. A functional association study of VEGF gene promoter polymorphisms with VEGF expression by stimulated pbm cells. Hum Immunol. 2003;64:S125.

    Article  Google Scholar 

  18. Stevens A, Soden J, Brenchley PE, Ralph S, Ray DW. Haplotype analysis of the polymorphic human vascular endothelial growth factor gene promoter. Cancer Res. 2003;63(4):812–6.

    CAS  PubMed  Google Scholar 

  19. Toi M, Inada K, Hoshina S, Suzuki H, Kondo S, Tominaga T. Vascular endothelial growth factor and platelet-derived endothelial cell growth factor are frequently coexpressed in highly vascularized human breast cancer. Clin Cancer Res. 1995;1(9):961–4.

    CAS  PubMed  Google Scholar 

  20. Jubb AM, Pham TQ, Hanby AM, Frantz GD, Peale FV, Wu TD, et al. Expression of vascular endothelial growth factor, hypoxia inducible factor 1alpha, and carbonic anhydrase IX in human tumours. J Clin Pathol. 2004;57(5):504–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gasparini G, Toi M, Gion M, Verderio P, Dittadi R, Hanatani M, et al. Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. J Natl Cancer Inst. 1997;89(2):139–47.

    Article  CAS  PubMed  Google Scholar 

  22. Linderholm B, Lindh B, Tavelin B, Grankvist K, Henriksson R. p53 and vascular-endothelial-growth-factor (VEGF) expression predicts outcome in 833 patients with primary breast carcinoma. Int J Cancer. 2000;89(1):51–62.

    Article  CAS  PubMed  Google Scholar 

  23. Linderholm BK, Lindahl T, Holmberg L, Klaar S, Lennerstrand J, Henriksson R, et al. The expression of vascular endothelial growth factor correlates with mutant p53 and poor prognosis in human breast cancer. Cancer Res. 2001;61(5):2256–60.

    CAS  PubMed  Google Scholar 

  24. Kushlinskii NE, Gershtein ES. Role of vascular endothelial growth factor during breast cancer. Bull Exp Biol Med. 2002;133(6):521–8.

    Article  CAS  PubMed  Google Scholar 

  25. Reich SJ, Fosnot J, Kuroki A, Tang W, Yang X, Maguire AM, et al. Small interfering RNA (siRNA) targeting VEGF effectively inhibits ocular neovascularization in a mouse model. Mol Vis. 2003;9:210–6.

    CAS  PubMed  Google Scholar 

  26. Jin Q, Hemminki K, Enquist K, Lenner P, Grzybowska E, Klaes R, et al. Vascular endothelial growth factor polymorphisms in relation to breast cancer development and prognosis. Clin Cancer Res. 2005;11(10):3647–53.

    Article  CAS  PubMed  Google Scholar 

  27. Schneider BP, Wang M, Radovich M, Sledge GW, Badve S, Thor A, et al. ECOG 2100. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol. 2008;26(28):4672–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kidd LR, Brock GN, VanCleave TT, Benford ML, Lavender NA, Kruer TL, et al. Angiogenesis-associated sequence variants relative to breast cancer recurrence and survival. Cancer Causes Control. 2010;21(10):1545–57.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Kong SY, Park JW, Lee JA, Park JE, Park KW, Hong EK, et al. Association between vascular endothelial growth factor gene polymorphisms and survival in hepatocellular carcinoma patients. Hepatology. 2007;46(2):446–55.

    Article  CAS  PubMed  Google Scholar 

  30. Nasr HB, Chahed K, Bouaouina N, Chouchane L. Functional vascular endothelial growth factor -2578 C/A polymorphism in relation to nasopharyngeal carcinoma risk and tumor progression. Clin Chim Acta. 2008;395(1–2):124–9.

    Article  PubMed  Google Scholar 

  31. Dassoulas K, Gazouli M, Rizos S, Theodoropoulos G, Christoni Z, Nikiteas N, et al. Common polymorphisms in the vascular endothelial growth factor gene and colorectal cancer development, prognosis, and survival. Mol Carcinog. 2009;48(6):563–9.

    Article  CAS  PubMed  Google Scholar 

  32. Kjaer-Frifeldt S, Fredslund R, Lindebjerg J, Hansen TF, Spindler KL, Jakobsen A. Danish Colorectal Cancer Group. Prognostic importance of VEGF-A haplotype combinations in a stage II colon cancer population. Pharmacogenomics. 2012;13(7):763–70.

    Article  CAS  PubMed  Google Scholar 

  33. Jaiswal PK, Tripathi N, Shukla A, Mittal RD. Association of single nucleotide polymorphisms in vascular endothelial growth factor gene with bladder cancer risk. Med Oncol. 2013;30(2):509.

    Article  PubMed  Google Scholar 

  34. Bruyere F, Hovens CM, Marson MN, D’Arcier BF, Costello AJ, Watier H, et al. VEGF polymorphisms are associated with an increasing risk of developing renal cell carcinoma. J Urol. 2010;184(4):1273–8.

    Article  CAS  PubMed  Google Scholar 

  35. Yang B, Cross DF, Ollerenshaw M, Millward BA, Demaine AG. Polymorphisms of the vascular endothelial growth factor and susceptibility to diabetic microvascular complications in patients with type 1 diabetes mellitus. J Diabetes Complications. 2003;17(1):1–6.

    Article  PubMed  Google Scholar 

  36. Buraczynska M, Ksiazek P, Baranowicz-Gaszczyk I, Jozwiak L. Association of the VEGF gene polymorphism with diabetic retinopathy in type 2 diabetes patients. Nephrol Dial Transplant. 2007;22(3):827–32.

    Article  CAS  PubMed  Google Scholar 

  37. Salvarani C, Boiardi L, Casali B, Olivieri I, Cantini F, Salvi F, et al. Vascular endothelial growth factor gene polymorphisms in Behçet’s disease. J Rheumatol. 2004;31(9):1785–9.

    CAS  PubMed  Google Scholar 

  38. Kamoun M, Houman MH, Hamzaoui A, Hamzaoui K. Vascular endothelial growth factor gene polymorphisms and serum levels in Behçet’s disease. Tissue Antigens. 2008;72(6):581–7.

    Article  CAS  PubMed  Google Scholar 

  39. Boiardi L, Casali B, Nicoli D, Farnetti E, Chen Q, Macchioni P, et al. Vascular endothelial growth factor gene polymorphisms in giant cell arteritis. J Rheumatol. 2003;30(10):2160–4.

    CAS  PubMed  Google Scholar 

  40. Breunis WB, Biezeveld MH, Geissler J, Ottenkamp J, Kuipers IM, Lam J, et al. Vascular endothelial growth factor gene haplotypes in Kawasaki disease. Arthritis Rheum. 2006;54(5):1588–94.

    Article  CAS  PubMed  Google Scholar 

  41. George GP, Mittal RD. Association of polymorphic variants of Vascular Endothelial Growth Factor (VEGF) gene in relation to risk and androgen therapy response in Prostate cancer patients of North India. 2011. http://www.ichg2011.org/cgi-bin/showdetail.pl?absno=10216. Accessed 16 May 2014.

  42. Prakash S, Prasad N, Sharma RK, Faridi RM, Agrawal S. Vascular endothelial growth factor gene polymorphisms in North Indian patients with end stage renal disease. Cytokine. 2012;58(2):261–6.

    Article  CAS  PubMed  Google Scholar 

  43. Lee SJ, Lee SY, Jeon HS, Park SH, Jang JS, Lee GY, et al. Vascular endothelial growth factor gene polymorphisms and risk of primary lung cancer. Cancer Epidemiol Biomarkers Prev. 2005;14(3):571–5.

    Article  CAS  PubMed  Google Scholar 

  44. Kataoka N, Cai Q, Wen W, Shu XO, Jin F, Gao YT, et al. Population-based case–control study of VEGF gene polymorphisms and breast cancer risk among Chinese women. Cancer Epidemiol Biomarkers Prev. 2006;15(6):1148–52.

    Article  CAS  PubMed  Google Scholar 

  45. Cacev T, Loncar B, Seiwerth S, Spaventi S, Kapitanovic S. Vascular endothelial growth factor polymorphisms -1154G/A and -460 C/T are not associated with VEGF mRNA expression and susceptibility to sporadic colon cancer. DNA Cell Biol. 2008;27(10):569–74.

    Article  CAS  PubMed  Google Scholar 

  46. Langsenlehner U, Wolf G, Langsenlehner T, Gerger A, Hofmann G, Clar H, et al. Genetic polymorphisms in the vascular endothelial growth factor gene and breast cancer risk. The Austrian “tumor of breast tissue: incidence, genetics, and environmental risk factors” study. Breast Cancer Res Treat. 2008;109(2):297–304.

    Article  CAS  PubMed  Google Scholar 

  47. Langsenlehner T, Langsenlehner U, Renner W, Krippl P, Mayer R, Wascher TC, et al. Single nucleotide polymorphisms and haplotypes in the gene for vascular endothelial growth factor and risk of prostate cancer. Eur J Cancer. 2008;44:1572–6.

    Article  CAS  PubMed  Google Scholar 

  48. Onen IH, Konac E, Eroglu M, Guneri C, Biri H, Ekmekci A. No association between polymorphism in the vascular endothelial growth factor gene at position -460 and sporadic prostate cancer in the Turkish population. Mol Biol Rep. 2008;35(1):17–22.

    Article  CAS  PubMed  Google Scholar 

  49. Zhai R, Liu G, Asomaning K, Su L, Kulke MH, Heist RS, et al. Genetic polymorphisms of VEGF, interactions with cigarette smoking exposure and esophageal adenocarcinoma risk. Carcinogenesis. 2008;29(12):2330–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Al-Moundhri MS, Al-Nabhani M, Burney IA, Al-Farsi AA, Al-Bahrani B. Gastric cancer risk predisposition and prognostic significance of vascular endothelial growth factor (VEGF) gene polymorphisms—a case–control study in an Omani population. Mol Carcinog. 2009;48(12):1170–6.

    Article  CAS  PubMed  Google Scholar 

  51. Maltese P, Canestrari E, Ruzzo A, Graziano F, Falcone A, Loupakis F, et al. VEGF gene polymorphisms and susceptibility to colorectal cancer disease in Italian population. Int J Colorectal Dis. 2009;24(2):165–70.

    Article  PubMed  Google Scholar 

  52. Talar-Wojnarowska R, Gasiorowska A, Olakowski M, Lekstan A, Lampe P, Smolarz B, et al. Vascular endothelial growth factor (VEGF) genotype and serum concentration in patients with pancreatic adenocarcinoma and chronic pancreatitis. J Physiol Pharmacol. 2010;61(6):711–6.

    CAS  PubMed  Google Scholar 

  53. Wall SJ, Jiang Y, Muschel RJ, DeClerck YA. Meeting report: proteases, extracellular matrix, and cancer: an AACR Special Conference in Cancer Research. Cancer Res. 2003;63(15):4750–5.

    CAS  PubMed  Google Scholar 

  54. Murakami M, Nguyen LT, Hatanaka K, Schachterle W, Chen PY, Zhuang ZW, et al. FGF-dependent regulation of VEGF receptor 2 expression in mice. J Clin Invest. 2011;121(7):2668–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Menendez D, Krysiak O, Inga A, Krysiak B, Resnick MA, Schonfelder G. A SNP in the flt-1 promoter integrates the VEGF system into the p53 transcriptional network. Proc Natl Acad Sci U S A. 2006;103(5):1406–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Menendez D, Inga A, Snipe J, Krysiak O, Schonfelder G, Resnick MA. A single-nucleotide polymorphism in a half-binding site creates p53 and estrogen receptor control of vascular endothelial growth factor receptor 1. Mol Cell Biol. 2007;27(7):2590–600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Rodrigues P, Furriol J, Tormo E, Ballester S, Lluch A, Eroles P. The single-nucleotide polymorphisms +936 C/T VEGF and -710 C/T VEGFR1 are associated with breast cancer protection in a Spanish population. Breast Cancer Res Treat. 2012;133(2):769–78.

    Article  CAS  PubMed  Google Scholar 

  58. Cancer incidence in state not so alarming, claims survey. Door-to-door study puts Punjab’s figures below the national average. In: The Tribune, Chandigarh, India. 2013. http://www.tribuneindia.com/2013/20130121/punjab.htm#3. Accessed 15 May 2014.

  59. Singletary SE, Allred C, Ashley P, Lawrence W. Bassett LW, Berry D, et al. (2002) Revision of the American Joint Committee on Cancer staging system for breast cancer. J Clin Oncol. 2002;20(17):3628–36

  60. Adeli K, Ogbonna G. Rapid purification of human DNA from whole blood for potential application in clinical chemistry laboratories. Clin Chem. 1990;36:261–4.

    CAS  PubMed  Google Scholar 

  61. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21:263–5.

    Article  CAS  PubMed  Google Scholar 

  62. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23(5):1011–27.

    Article  CAS  PubMed  Google Scholar 

  63. Salven P, Perhoniemi V, Tykka H, Maenpaa H, Joensuu H. Serum VEGF levels in women with a benign breast tumor or breast cancer. Breast Cancer Res Treat. 1999;53(2):161–6.

    Article  CAS  PubMed  Google Scholar 

  64. Heer K, Kumar H, Read JR, Fox JN, Monson JR, Kerin MJ. Serum vascular endothelial growth factor in breast cancer: its relation with cancer type and estrogen receptor status. Clin Cancer Res. 2001;7(11):3491–4.

    CAS  PubMed  Google Scholar 

  65. Pande D, Negi R, Khanna S, Khanna R, Khanna HD. Vascular endothelial growth factor levels in relation to oxidative damage and antioxidant status in patients with breast cancer. J Breast Cancer. 2011;14(3):181–4.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Kapahi R, Manjari M, Uppal MS, Singh NR, Sambyal V, Guleria K. Association of -2549 insertion/deletion polymorphism of vascular endothelial growth factor with breast cancer in North Indian patients. Genet Test Mol Biomarkers. 2013;17(3):242–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Shahbazi M, Fryer AA, Pravica V, Brogan IJ, Ramsay HM, Hutchinson IV, et al. Vascular endothelial growth factor gene polymorphisms are associated with acute renal allograft rejection. J Am Soc Nephrol. 2002;13(1):260–4.

    CAS  PubMed  Google Scholar 

  68. Krippl P, Langsenlehner U, Renner W, Yazdani-Biuki B, Wolf G, Wascher TC, et al. A common 936 C/T gene polymorphism of vascular endothelial growth factor is associated with decreased breast cancer risk. Int J Cancer. 2003;106(4):468–71.

    Article  CAS  PubMed  Google Scholar 

  69. He Y, Ni J, Chen S, Jiang Y, Jia S, Gao Y. The vascular endothelial growth factor-2549 insertion/deletion polymorphism is not associated with susceptibility to hepatocellular carcinoma in Chinese. DNA Cell Biol. 2010;29(7):393–6.

    Article  CAS  PubMed  Google Scholar 

  70. Ungerback J, Elander N, Dimberg J, Soderkvist P. Analysis of VEGF polymorphisms, tumor expression of VEGF mRNA and colorectal cancer susceptibility in a Swedish population. Mol Med Rep. 2009;2(3):435–9.

    PubMed  Google Scholar 

  71. Schneider BP, Radovich M, Sledge GW, Robarge JD, Li L, Storniolo AM, et al. Association of polymorphisms of angiogenesis genes with breast cancer. Breast Cancer Res Treat. 2008;111(1):157–63.

    Article  CAS  PubMed  Google Scholar 

  72. Zhang L, Zhang G, Wang P, Gong J, Cao Y, Tang L. Association of vascular endothelial growth factor -2578C/A gene polymorphism in Chinese patients with colon cancer. Genet Test Mol Biomarkers. 2011;15(3):117–21.

    Article  CAS  PubMed  Google Scholar 

  73. Li Y, Liang J, Liu X, Liu H, Yin B, Xiao J, et al. Correlation of polymorphisms of the vascular endothelial growth factor gene and the risk of lung cancer in an ethnic Han group of North China. Exp Ther Med. 2012;3(4):673–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Koukourakis MI, 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.

    Article  PubMed  Google Scholar 

  75. Wang T, Hu K, Ren J, Zhu Q, Wu G, Peng G. Polymorphism of VEGF-2578C/A associated with the risk and aggressiveness of nasopharyngeal carcinoma in a Chinese population. Mol Biol Rep. 2010;37(1):59–65.

    Article  CAS  PubMed  Google Scholar 

  76. Hsiao PJ, Lu MY, Chiang FY, Shin SJ, Tai YD, Juo SH. Vascular endothelial growth factor gene polymorphisms in thyroid cancer. J Endocrinol. 2007;195(2):265–70.

    Article  CAS  PubMed  Google Scholar 

  77. Jacobs EJ, Feigelson HS, Bain EB, Brady KA, Rodriguez C, Stevens VL, et al. Polymorphisms in the vascular endothelial growth factor gene and breast cancer in the Cancer Prevention Study II cohort. Breast Cancer Res. 2006;8(2):R22.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Howell WM, Bateman AC, Turner SJ, Collins A, Theaker JM. Influence of vascular endothelial growth factor single nucleotide polymorphisms on tumour development in cutaneous malignant melanoma. Genes Immun. 2002;3(4):229–32.

    Article  CAS  PubMed  Google Scholar 

  79. Tzanakis N, Gazouli M, Rallis G, Giannopoulos G, Papaconstantinou I, Theodoropoulos G, et al. Vascular endothelial growth factor polymorphisms in gastric cancer development, prognosis, and survival. J Surg Oncol. 2006;94(7):624–30.

    Article  CAS  PubMed  Google Scholar 

  80. Ke Q, Liang J, Wang LN, Hu ZB, Jin GF, Zhou Y, et al. Potentially functional polymorphisms of the vascular endothelial growth factor gene and risk of gastric cancer. Mol Carcinog. 2008;47(8):647–51.

    Article  CAS  PubMed  Google Scholar 

  81. Hofmann G, Langsenlehner U, Renner W, Langsenlehner T, Yazdani-Biuki B, Clar H, et al. Common single nucleotide polymorphisms in the vascular endothelial growth factor gene and colorectal cancer risk. J Cancer Res Clin Oncol. 2008;134(5):591–5.

    Article  CAS  PubMed  Google Scholar 

  82. Li Y, Wang Y, Kang S, Wang N, Zhou RM, Duan YN, et al. Association of vascular endothelial growth factor gene polymorphisms with susceptibility to epithelial ovarian cancer. Int J Gynecol Cancer. 2010;20(5):717–23.

    Article  PubMed  Google Scholar 

  83. Saenz-Lopez P, Vazquez F, Cozar JM, Carretero R, Garrido F, Ruiz-Cabello F. VEGF polymorphisms are not associated with an increased risk of developing renal cell carcinoma in Spanish population. Hum Immunol. 2013;74(1):98–103.

    Article  CAS  PubMed  Google Scholar 

  84. Konac E, Onen HI, Metindir J, Alp E, Biri AA, Ekmekci A. Lack of association between -460 C/T and 936 C/T of the vascular endothelial growth factor and angiopoietin-2 exon 4G/A polymorphisms and ovarian, cervical, and endometrial cancers. DNA Cell Biol. 2007;26(7):453–63.

    Article  CAS  PubMed  Google Scholar 

  85. Tavakkoly-Bazzaz J, Amoli MM, Pravica V, Chandrasecaran R, Boulton AJ, Larijani B, et al. VEGF gene polymorphism association with diabetic neuropathy. Mol Biol Rep. 2010;37(7):3625–30.

    Article  CAS  PubMed  Google Scholar 

  86. Szeto CC, Chow KM, Poon P, Szeto CY, Wong TY, Li PK. Genetic polymorphism of VEGF: impact on longitudinal change of peritoneal transport and survival of peritoneal dialysis patients. Kidney Int. 2004;65(5):1947–55.

    Article  CAS  PubMed  Google Scholar 

  87. Willett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL, Tong RT, et al. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med. 2004;10(2):145–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Jain RK. Antiangiogenic therapy for cancer: current and emerging concepts. Oncology (Williston Park). 2005;19(4 Suppl 3):7–16.

    Google Scholar 

  89. Suganthalakshmi B, Anand R, Kim R, Mahalakshmi R, Karthikprakash S, Namperumalsamy P, et al. Association of VEGF and eNOS gene polymorphisms in type 2 diabetic retinopathy. Mol Vis. 2006;12:336–41.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank the patients and control individuals for taking part in this study. This study was supported by the DBT grant BT/PR 13252/GBD/27/236/2009 sanctioned to KG and VS. Research fellowship (No. 3/1/3/JRF-2012/HRD) to RK from ICMR is duly acknowledged. We are thankful to Dr. Geeta Sharma, Principal, Sri Guru Ram Das Institute of Medical Sciences and Research, Vallah, Amritsar, Punjab, for their help in providing access to patients and facilities for execution of research work.

Conflicts of interest

None

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kamlesh Guleria.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kapahi, R., Guleria, K., Sambyal, V. et al. Association of VEGF and VEGFR1 polymorphisms with breast cancer risk in North Indians. Tumor Biol. 36, 4223–4234 (2015). https://doi.org/10.1007/s13277-015-3059-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-3059-1

Keywords

Navigation