Vascular endothelial growth factor (VEGF) polymorphism and increased risk of epithelial ovarian cancer.

Introduction: Angiogenesis (AG) is essential for epithelial ovarian cancer (EOC) development. Vascular endothelial growth factor (VEGF), encoded by the VEGF gene, and endostatin, the product of the COL18A1 gene, act as a potent promoter and an inhibitor of AG, respectively. In the present study, we tested whether VEGF C936T and COL18A1 D104N polymorphisms alter the risk of EOC.

Methods: Genomic DNA from 131 EOC patients and 137 controls were analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. The differences between groups were analyzed by χ (2) or Fisher's exact test and logistic regression analysis.

Results: The frequency of the VEGF 936CC genotype was higher in patients than in controls (84.8% vs. 75.3%, P = 0.03). Individuals with respective genotypes had a 1.98 (95% CI 1.04-3.78)-fold increased risk of EOC than those with the remaining genotypes. An excess of VEGF 936CC plus COL18A1 DN genotype was seen in patients when compared to controls (48.6% vs. 30.5%); however, only a tendency toward a statistically significant difference in genotype frequencies was found in the study (P = 0.06), reflecting a trend toward an increased risk of 2.44 for EOC in carriers of the combined genotype.

Conclusion: Our data present, for the first time, preliminary evidence that VEGF C936T alone or combined with the COL18A1 D104N polymorphism of AG constitutes an important inherited EOC determinant.