Association of <i>VEGFA</i> gene rs2010963 polymorphism with cervical cancer and its progression

Abstract

Background: Cervical cancer is the most common type of female genital malignancies. In Russia, its incidence is 17 to 19 cases per 100,000 of female population. Cervical cancer is characterized by high activity, rapid development of radio/chemoresistance and unfavorable prognosis. To assess the risk of recurrence, metastasis and choice of the optimal treatment strategy, factors related to the disease progression are under study. Vascular endothelial growth factor (VEGF) overexpression is related to tumor angiogenesis and poor outcome in various cancer types, including cervical cancer. Aim: To study an association between the rs2010963 polymorphism of the VEGFA gene and risk of development and progression of cervical cancer. Materials and methods: This case-control study included 120 women (aged 49 [42; 65] years) with cervical cancer stage I-II and 112 women without cervical or other types of cancer. Based on the results of histological examination, two subgroups were formed: the one with tumor emboli (TE+) in the tumor vasculature and surrounding tissues (n = 41, 34.17%) and the other without tumor emboli (TE-) (n = 79, 65.83%). The polymorphic DNA loci of the rs2010963 VEGFA gene were analyzed by real time polymerase chain reaction. Results: In the patients, cervical cancer has associated with the VEGFA gene allelic polymorphism rs2010963 (χ2 = 5.47; p = 0.021). The minor C allele increased risk of cervical cancer by 1.6-fold (odds ratio (OR) 1.58, 95% confidence interval (CI) 1.08-2.31), and the ancestral G allele reduced the cervical cancer probability (OR 0.63, 95% CI 0.43-0.93). The genotypes distribution in the dominant model (GG and GC + CC) confirmed the association of the rs2010963 VEGFA gene polymorphism with cervical cancer (χ2 = 4.73; p = 0.031), specifically, if there was a minor C allele in the genotype (GC + CC). We found that the association of the rs2010963 VEGFA gene polymorphism with TE in the tumor vessels and surrounding tissues was a predictor of unfavorable progression and metastasis of cervical cancer (χ2 = 3.94; p = 0.049). The minor C allele increased the risk of TE by 1.7-fold (OR 1.72, 95% CI 1.004-2.98), whereas the ancestral G allele reduced this chance (OR 0.58, 95% CI 0.34-0.996). Conclusion: The C allele of the rs2010963 polymorphism of the VEGFA gene is a risk factor for cervical cancer, as well as a risk factor for the development of tumor emboli.

Keywords

• cervical cancer
• tumor emboli
• polymorphism
• vegfa gene