Abstract
6050 Background: VEGF-A is a potent inducer of endothelial cell growth and tumor neo-vascularisation. We previously reported that tumoral VEGF-A expression is linked to overall survival in HNCP (Onesto et al. Br J Cancer 2006). The present purpose was to extend this study by analyzing VEGF-A gene polymorphisms since functional VEGF-A polymorphisms associated with serum VEGF-A and risk of cancer have been described. Methods: VEGF-A polymorphisms in position (relative to translation initiation) −2578C>A (promoter region), − 1498T>C (promoter region), −634G>C (5’UTR) and 936C>T (3’UTR) were analyzed (PCR-RFLP) in tumoral genomic DNA from 49 Caucasian HNCP (34 men, 15 women; 16 T1-T2, 33 T3-T4; 31% N0). Tumoral VEGF-A expression was measured with an ELISA kit. Results: Genotype distributions agreed with those predicted by the Hardy-Weinberg equilibrium. A linkage disequilibrium was observed between −2578C>A and −634G>C (p<0.001) as well as between −2578C>A and −1498T>C (p<0.001). Of note, tumoral VEGF-A expression was influenced by the 936C>T polymorphism, with a median at 540 pg/mg in CT+TT patients (N = 5) versus 940 pg/mg in CC patients (N = 44) (p = 0.064). VEGF-A expression was not related to any other polymorphisms. None of the analyzed polymorphisms was linked to node involvement or to tumor size. Unlike tumoral VEGF-A expression, the analyzed genotypes were not related to patient survival. Conclusions: In addition to the known influence of tumor hypoxia, the present data suggest that the 936C>T polymorphism can modulate tumoral VEGF expression, with the presence of the T allele associated with decreased VEGF-A expression. Determination of this germinal polymorphism may thus provide an easily accessible test that deserves further investigation as a potential factor to aid anti-angiogenic treatment selection. No significant financial relationships to disclose.
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