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
