VEGF polymorphisms in early cervical cancer susceptibility, angiogenesis, and survival

Abstract

Objective. Vascular endothelial growth factor (VEGF) plays an important role in cervical carcinogenesis. We hypothesized that VEGF genetic polymorphisms may affect cancer susceptibility, angiogenesis, and survival in patients with early cervical cancer. Methods. Among 215 healthy subjects and 199 early cervical cancer patients who were treated with surgical resection, we specifically investigated four genetic polymorphisms within the VEGF gene (-2578C>A, -460 T>C, +405G>C, and +936C>T). VEGF and CD31 microvessel density (MVD) were measured using tissue microarrays constructed from 117 patients who had available tissue. Results. Risk of cervical cancer was decreased in subjects with the VEGF -2578A/A genotype (adjusted OR = 0.39, 95% CI 0.16-0.96). Angiogenesis measured by CD31 MVD was significantly decreased in patients with the VEGF +405C/C genotype and VEGF -2578C - -460T - + 405C haplotype (recessive model; adjusted OR=0.32, 95% CI 0.11-0.99, equally). Moreover, VEGF +405C/C and VEGF -2578C - 460 T - +405C haplotype were significantly related to shorter disease-free survival (adjusted HR = 3.18, 95% CI 1.13-8.94, equally) and overall survival (adjusted HR=8.86, 95% CI 1.40-56.08, equally) by multiple Cox regression analysis. Conclusion. Polymorphisms of VEGF genes may affect cancer susceptibility and survival of early cervical cancer by modulating tumor angiogenesis. Prospective study among homogeneously treated patients is warranted. (C) 2010 Elsevier Inc. All rights reserved.