ABSTRACT. We conducted a case-control study in a Chinese population, and assessed whether the VEGF -634G/C, +936C/T, and +1612G/A polymorphisms could affect the risk of osteosarcoma and its association with environmental factors. A total of 180 consecutive osteosarcoma patients and 360 controls were included in our study. The genotypes of VEGF -634G/C, +936C/T, and +1612G/A were determined by the polymerase chain reaction-restriction fragment length polymorphism assay. Conditional logistic regression analyses showed that subjects carrying the GG genotype and the G allele of VEGF -634G/C were significantly associated with increased risk of osteosarcoma compared to those with the CC genotype; the ORs (95%CIs) were 2.28 (1.31-3.96) and 1.51 (1.16-1.97) for the GG genotype and G allele, respectively. We found that the GG genotype of VEGF -634G/C was associated with a significantly increased risk 8284 G. Zhang et al. ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (3): 8283-8289 (2015) of osteosarcoma in patients of either gender with younger age and a family history of cancer. In summary, this study found that the VEGF -634G/C gene polymorphism was associated with an increased risk of osteosarcoma.