Skip to main content

Advertisement

Log in

The low VEGF production allele of the +936C/T polymorphism is strongly associated with increased risk for oral cancer

  • Rapid Communication
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Based on the well-established role of vascular endothelial growth factor (VEGF) in tumor-associated angiogenesis in several cancer types and its undefined role in oral oncogenesis, we investigated the possible association of an expression-regulating polymorphism (+936C/T) with risk for oral squamous cell carcinoma (OSCC).

Methods

We studied the allele frequencies of the +936C/T polymorphism in DNA samples of 144 patients with OSCC and 153 healthy controls matched by age, gender and ethnicity, using restriction fragment length polymorphism typing analysis.

Results

The low-expression T allele was significantly increased in the total patient group compared to controls (P = 0.008), due to a significant over-representation of C/T heterozygotes compared to C/C homozygotes (P = 0.007). The same pattern was observed in most patient subgroups and more noticeably in patients with a positive family history of cancer (P = 0.001). Interestingly, the increase in T allele frequency was only significant in patients at cancer stages I and II (P = 0.006).

Conclusions

This study clearly indicates that the low-VEGF-production T allele is strongly associated with increased risk for OSCC. In addition, the impressive T allele frequency increment in patients with a positive family cancer history suggests that this allele may also be involved in other malignancies. The fact that this significant increase was observed only in patients with early cancer stages may imply that low VEGF levels might hinder subsequent tumorigenesis. Our findings might be the result of either unidentified properties of the +936 C/T polymorphism or of a strong linkage disequilibrium between this polymorphism and another genetic locus.

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.

Institutional subscriptions

References

  • Abe A, Sato K, Habuchi T, Wang L, Li Z, Tsuchiya N, Ohyama C, Satoh S, Ogawa O, Kato T (2002) Single nucleotide polymorphisms in the 3′ untranslated region of vascular endothelial growth factor gene in Japanese population with or without renal cell carcinoma. Tohoku J Exp Med 198:181–190

    Article  PubMed  CAS  Google Scholar 

  • Carlile J, Harada K, Baillie R, Macluskey M, Chisholm DM, Ogden GR, Schor SL, Schor AM (2001) Vascular endothelial growth factor (VEGF) expression in oral tissues: possible relevance to angiogenesis, tumour progression and field cancerisation. J Oral Pathol Med 30:449–457

    Article  PubMed  CAS  Google Scholar 

  • Eroglu A, Gulec S, Akar N (2006) Vascular endothelial growth factor C936T polymorphism in cancer patients with thrombosis. Am J Hematol 82(2):174

    Article  Google Scholar 

  • Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25:581–611

    Article  PubMed  CAS  Google Scholar 

  • Jacobs EJ, Feigelson HS, Bain EB, Brady KA, Rodriguez C, Stevens VL, Patel AV, Thun MJ, Calle EE (2006) Polymorphisms in the vascular endothelial growth factor gene and breast cancer in the Cancer Prevention Study II cohort. Breast Cancer Res 8:R22

    Article  PubMed  Google Scholar 

  • Jin Q, Hemminki K, Enquist K, Lenner P, Grzybowska E, Klaes R, Henriksson R, Chen B, Pamula J, Pekala W, Zientek H, Rogozinska-Szczepka J, Utracka-Hutka B, Hallmans G, Forsti A (2005) Vascular endothelial growth factor polymorphisms in relation to breast cancer development and prognosis. Clin Cancer Res 11:3647–3653

    Article  PubMed  CAS  Google Scholar 

  • Johnstone S, Logan RM (2006) The role of vascular endothelial growth factor (VEGF) in oral dysplasia and oral squamous cell carcinoma. Oral Oncol 42:337–342

    Article  PubMed  CAS  Google Scholar 

  • Kataoka N, Cai Q, Wen W, Shu XO, Jin F, Gao YT, Zheng W (2006) Population-based case-control study of VEGF gene polymorphisms and breast cancer risk among Chinese women. Cancer Epidemiol Biomarkers Prev 15:1148–1152

    Article  PubMed  CAS  Google Scholar 

  • Krippl P, Langsenlehner U, Renner W, Yazdani-Biuki B, Wolf G, Wascher TC, Paulweber B, Haas J, Samonigg H (2003) A common 936 C/T gene polymorphism of vascular endothelial growth factor is associated with decreased breast cancer risk. Int J Cancer 106:468–471

    Article  PubMed  CAS  Google Scholar 

  • Lee SJ, Lee SY, Jeon HS, Park SH, Jang JS, Lee GY, Son JW, Kim CH, Lee WK, Kam S, Park RW, Park TI, Kang YM, Kim IS, Jung TH, Park JY (2005) Vascular endothelial growth factor gene polymorphisms and risk of primary lung cancer. Cancer Epidemiol Biomarkers Prev 14:571–575

    Article  PubMed  CAS  Google Scholar 

  • Lu H, Shu XO, Cui Y, Kataoka N, Wen W, Cai Q, Ruan ZX, Gao YT, Zheng W (2005) Association of genetic polymorphisms in the VEGF gene with breast cancer survival. Cancer Res 65:5015–5019

    Article  PubMed  CAS  Google Scholar 

  • McDowell JD (2006) An overview of epidemiology and common risk factors for oral squamous cell carcinoma. Otolaryngol Clin North Am 39:277–294

    Article  PubMed  Google Scholar 

  • Ranieri G, Labriola A, Achille G, Florio G, Zito AF, Grammatica L, Paradiso A (2002) Microvessel density, mast cell density and thymidine phosphorylase expression in oral squamous carcinoma. Int J Oncol 21:1317–1323

    PubMed  CAS  Google Scholar 

  • Renner W, Kotschan S, Hoffmann C, Obermayer-Pietsch B, Pilger E (2000) 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 37:443–448

    Article  PubMed  CAS  Google Scholar 

  • Roberts WG, Palade GE (1995) Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci 108(Pt 6):2369–2379

    PubMed  CAS  Google Scholar 

  • Sciacca FL, Ciusani E, Silvani A, Corsini E, Frigerio S, Pogliani S, Parati E, Croci D, Boiardi A, Salmaggi A (2004) Genetic and plasma markers of venous thromboembolism in patients with high grade glioma. Clin Cancer Res 10:1312–1317

    Article  PubMed  CAS  Google Scholar 

  • Schimming R, Reusch P, Kuschnierz J, Schmelzeisen R (2004) Angiogenic factors in squamous cell carcinoma of the oral cavity: do they have prognostic relevance? J Craniomaxillofac Surg 32:176–181

    PubMed  Google Scholar 

  • Sfar S, Hassen E, Saad H, Mosbah F, Chouchane L (2006) Association of VEGF genetic polymorphisms with prostate carcinoma risk and clinical outcome. Cytokine 35:21–28

    Article  PubMed  CAS  Google Scholar 

  • Shintani S, Li C, Ishikawa T, Mihara M, Nakashiro K, Hamakawa H (2004) Expression of vascular endothelial growth factor A, B, C, and D in oral squamous cell carcinoma. Oral Oncol 40:13–20

    Article  PubMed  CAS  Google Scholar 

  • Tzanakis N, Gazouli M, Rallis G, Giannopoulos G, Papaconstantinou I, Theodoropoulos G, Pikoulis E, Tsigris C, Karakitsos P, Peros G, Nikiteas N (2006) Vascular endothelial growth factor polymorphisms in gastric cancer development, prognosis, and survival. J Surg Oncol 94:624–630

    Article  PubMed  CAS  Google Scholar 

  • Vairaktaris E, Yapijakis C, Derka S, Vassiliou S, Serefoglou Z, Vylliotis A, Wiltfang J, Springer I, Nkenke E, Kessler P, Neukam FW (2006a) Association of platelet glycoprotein Ia polymorphism with minor increase of risk for oral cancer. Eur J Surg Oncol 32:455–457

    Article  PubMed  CAS  Google Scholar 

  • Vairaktaris E, Yapijakis C, Kessler P, Vylliotis A, Ries J, Wiltfang J, Vassiliou S, Derka S, Neukam FW (2006b) Methylenetetrahydrofolate reductase polymorphism and minor increase of risk for oral cancer. J Cancer Res Clin Oncol 132:219–222

    Article  PubMed  CAS  Google Scholar 

  • Vairaktaris E, Yapijakis C, Serefoglou Z, Vylliotis A, Ries J, Nkenke E, Wiltfang J, Derka S, Vassiliou S, Springer I, Kessler P, Neukam FW (2006c) Plasminogen activator inhibitor-1 polymorphism is associated with increased risk for oral cancer. Oral Oncol 42:888–892

    Article  PubMed  CAS  Google Scholar 

  • Vairaktaris E, Yapijakis C, Serefoglou Z, Derka S, Vassiliou S, Nkenke E, Vylliotis A, Wiltfang J, Avgoustidis D, Critselis E, Neukam FW, Patsouris E (2006d) The interleukin-8 (-251A/T) polymorphism is associated with increased risk for oral squamous cell carcinoma. Eur J Surg Oncol 33(4):504–507

    Article  PubMed  Google Scholar 

  • Vairaktaris E, Yapijakis C, Derka S, Serefoglou Z, Vassiliou S, Nkenke E, Ragos V, Vylliotis A, Spyridonidou S, Tsigris C, Yannopoulos A, Tesseromatis C, Neukam FW, Patsouris E (2007) Association of matrix metalloproteinase-1 (-1607 1G/2G) polymorphism with increased risk for oral squamous cell carcinoma. Anticancer Res 27:459–464

    PubMed  CAS  Google Scholar 

  • Verheul HM, Jorna AS, Hoekman K, Broxterman HJ, Gebbink MF, Pinedo HM (2000) Vascular endothelial growth factor-stimulated endothelial cells promote adhesion and activation of platelets. Blood 96:4216–4221

    PubMed  CAS  Google Scholar 

  • Yamamori M, Sakaeda T, Nakamura T, Okamura N, Tamura T, Aoyama N, Kamigaki T, Ohno M, Shirakawa T, Gotoh A, Kuroda Y, Matsuo M, Kasuga M, Okumura K (2004) Association of VEGF genotype with mRNA level in colorectal adenocarcinomas. Biochem Biophys Res Commun 325:144–150

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by EPEAEK “Pythagoras” grant 70/3/7391 of the Greek Secretariat of Research and Technology to E.V.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to E. Vairaktaris.

Additional information

C.Yapijakis and E. Vairaktaris have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yapijakis, C., Vairaktaris, E., Vassiliou, S. et al. The low VEGF production allele of the +936C/T polymorphism is strongly associated with increased risk for oral cancer. J Cancer Res Clin Oncol 133, 787–791 (2007). https://doi.org/10.1007/s00432-007-0240-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-007-0240-y

Keywords

Navigation