Associations between single-nucleotide polymorphisms of the VEGF gene and long-term prognosis of oral squamous cell carcinoma

J Oral Pathol Med. 2013 May;42(5):374-81. doi: 10.1111/jop.12026. Epub 2012 Dec 10.

Abstract

Introduction: Functional polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) are associated with the incidence of oral squamous cell carcinoma (OSCC). An impact of VEGF-SNPs on prognosis of OSCC patients seems possible. Therefore, correlations between prognostic parameters of OSCC patients and five VEGF-SNPs were determined.

Materials and methods: In a retrospective long-term study, in 113 OSCC patients that underwent curative resections, five VEGF-SNPs (-1154 G/A, +405 G/C, +936 C/T, -2578 C/A, and -460 C/T) were analyzed. Associations between SNPs and prognosis (incidence of local recurrent disease, second cancer, metastases, death, total disease-free survival) were examined.

Results: After a mean follow-up time of 57.6 months, 32 patients had local recurrences; 15 patients had second cancer, 15 patients metastases, and 23 patients died. The mean disease-free survival was 43.1 months. A significant increased incidence of OSCC in smokers with the VEGF -2578 A/C and -460 C/T SNP was seen (each P < 0.0001). In univariate analysis, patients with advanced OSCCs (T > 2 or N > 0) together with the -1154 A/A allele had a significant worse survival and a worse disease-free survival (both P < 0.04). The same was seen for the +405 G/G SNP (both P = 0.002). In multivariate analysis, only the negative influence of the +405 G/G SNP on survival in advanced OSCCs (T > 2) could be confirmed (P = 0.002).

Discussion: Possible reciprocal interactions between smoking and VEGF-SNP function were observed. Multivariate analysis confirmed the VEGF +405 G/G genotype to be associated with poor survival in advanced OSCCs; a further use of this haplotype as biomarker has to be discussed.

MeSH terms

  • Adenosine
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / secondary
  • Carcinoma, Squamous Cell / surgery*
  • Cytosine
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Gene Frequency / genetics
  • Genotype
  • Guanine
  • Haplotypes
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / surgery*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Neoplasms, Second Primary / pathology
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Retrospective Studies
  • Smoking
  • Survival Rate
  • Thymine
  • Vascular Endothelial Growth Factor A / genetics*
  • Young Adult

Substances

  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Guanine
  • Cytosine
  • Adenosine
  • Thymine