The low VEGF production allele of the +936C/T polymorphism is strongly associated with increased risk for oral cancer.
OBJECTIVE
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.
Yapijakis
C
C
Department of Oral and Maxillofacial Surgery, University of Athens Medical School, Vas. Sofias 93 & Dim. Soutsou 1, Athens, 11521, Greece.
Vairaktaris
E
E
Vassiliou
S
S
Vylliotis
A
A
Nkenke
E
E
Nixon
A M
AM
Derka
S
S
Spyridonidou
S
S
Vorris
E
E
Neukam
F
F
Patsouris
E
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D042461:Vascular Endothelial Growth Factor A