title: Associations between single-nucleotide polymorphisms of the VEGF gene and long-term prognosis of oral squamous cell carcinoma.
abstract: BACKGROUND
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Harvard Medical School, Boston, MA, USA. peer.kaemmerer@gmx.de
authors.forename: P W
authors.initials: PW
authors.lastname: Kämmerer
authors.forename: F P
authors.initials: FP
authors.lastname: Koch
authors.forename: E
authors.initials: E
authors.lastname: Schiegnitz
authors.forename: V V
authors.initials: VV
authors.lastname: Kumar
authors.forename: M
authors.initials: M
authors.lastname: Berres
authors.forename: T
authors.initials: T
authors.lastname: Toyoshima
authors.forename: B
authors.initials: B
authors.lastname: Al-Nawas
authors.forename: J
authors.initials: J
authors.lastname: Brieger
mesh_terms: D000241:Adenosine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000556:secondary / Q000601:surgery*; D003596:Cytosine; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006147:Guanine; D006239:Haplotypes; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000601:surgery*; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D012907:Smoking; D015996:Survival Rate; D013941:Thymine; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D055815:Young Adult
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D006147:Guanine; D003596:Cytosine; D000241:Adenosine; D013941:Thymine