Vascular endothelial growth factor G+405C polymorphism may contribute to the risk of developing papillary thyroid carcinoma.

Background: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Vascular endothelial growth factor (VEGF) is a mediator implicated with cell proliferation, differentiation and migration, and monocyte/macrophage chemotaxis. In present study, we aimed to investigate the relationship between VEGF gene polymorphisms (G+405C, T-460C, and A-2578C) and PTC susceptibility.

Methods: DNA was isolated from peripheral blood leukocytes of 127 patients with PTC and 203 healthy controls. Genotyping was performed by real-time PCR. Association of genotypes with susceptibility of PTC was analyzed with multivariate logistic regression adjusted for age, gender and smoking status.

Results And Conclusion: In G+405C polymorphism, the frequencies of C allele (related with increased VEGF production) and combined CG+CC genotype were found to be higher (3.5 and 5-fold, respectively) among patients with PTC than controls (P<.001). However, VEGF T-460C and A-2578C polymorphisms are not associated with PTC risk. There was no relationship between VEGF polymorphisms and clinical/laboratory parameters of PTC. Haplotype analysis demonstrated that there was a strong linkage disequilibrium (LD) between -460/-2578 (D'=.89, r =.79), weak LD between +405/-460 (D'=.422, r =.035), and +405/-2578 (D'=.43, r =.038) locuses. Additionally, the +405/-460/-2578 GTA haplotype was found to be protective, whereas CTA haplotype to be related with increased PTC risk. As a conclusion, we suggest that VEGF G+405C polymorphism is associated with increased risk of PTC.