Abstract
Objective:The VEGF in low oxygen conditions are reported to prolong the survival of malignant cell, and thus this gene has a critical role in tumor growth and invasion as well as development of malignant tumor. We aimed to assess the association between the six common SNPs and the risk of osteosarcoma, and their association with environmental factors.Methods:176 subjects with osteosarcoma and 176 gender- and sex-matched healthy control individuals were enrolled into our study. The VEGF -2578C/A, -1156G/A, +1612G/A, +936C/T, -634G/C and -460T/C gene polymorphisms were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay according to manufacturer’s instructionsResults:By conditional logistic regression analysis, AA and CA+AA genotypes of VEGF -2578C/A were associated with significant increased risk of osteosarcoma compared with CC genotype, and the ORs(95%CI) were 2.32(1.18-4.60) and 1.68(1.07-2.64), respectively. Moreover, individuals with CC and TC+CC genotypes of VEGF-460T/C had significant increased risk of osteosarcoma compared with those carrying with the TT genotype, and ORs(95%CI) were 2.15(1.10-4.21) and 1.60(1.0-2.58), respectively. By stratified analysis, we did not find statistically significant associated between VEGF -2578C/A and -460T/C gene polymorphisms and cancer risk by stratification analysis.Conclusion:Our results suggested that VEGF -2578C/A and -460T/C gene polymorphisms may be association with an increased risk of osteosarcoma.
Highlights
Osteosarcoma is the most common type of primary bone cancer, and this cancer is a malignant tumor arising from mesenchymal tissues
Increasing evidences have reported that genetic polymorphisms play an important role in development of osteosarcoma, especially for angiogenesis genes.[4,5,6]
It is well known that angiogenesis plays an important role in the process of tumor growth, and can affect the tumor invasion and metastasis.[19,20]
Summary
Osteosarcoma is the most common type of primary bone cancer, and this cancer is a malignant tumor arising from mesenchymal tissues. It is well known that vascular endothelial growth factors (VEGF), a potent angiogenic growth factor, plays an important role in altering proliferation to inflammatory and ischemic processes.[10,11] The human VEGF is located at 6p21.1, and it is highly polymorphic in the promoter 5’untranslated region (5’-UTR) and 3’UTR.[12,13,14] It is reported that single nucleotide polymorphisms (SNPs) in VEGF could regulate the expression of this gene through altering initiation of transcription and internal initiation of translation.[15] Several SNPs in the 5’-UTR and 3’UTR were reported to be associated with alteration of VEGF protein production, including -2578C/A, -1156G/A, +1612G/A, +936C/T and -634G/C as well as -460T/C. Two studies have assessed the role of common VEGF polymorphisms in the risk of osteosarcoma in a Chinese population.[16,17] the aim of this present study was to assess the association between the six common SNPs and the risk of osteosarcoma, and their association with environmental factors
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