The -1154 G/A VEGF gene polymorphism is associated with the incidence of basal cell carcinoma in patients from northern Poland.

Abstract

Vascular endothelial growth factor (VEGF) is believed to play a crucial role in neoplastic angiogenesis. Although the genetic background of basal cell carcinoma (BCC) has been analyzed in some papers, the mechanism of BCC pathogenesis is not fully understood. To the best of our knowledge, VEGF gene polymorphisms have not yet been explored. The aim of the study was to asses the frequency of three polymorphisms in the VEGF gene (−1154 G/A, −460 T/C and +405 G/C) in patients of Polish origin with BCC and control group. In addition, VEGF serum levels of patients with BCC and controls were measured. The study involved 180 patients (96 women, 84 men) with BCC and a mean age of 68.9 ± 11.8, and 215 healthy age- and sex-matched volunteers. The VEGF polymorphisms at positions −1154 and +405 were analyzed using the amplification refractory mutation system polymerase chain reaction method. To assess the VEGF gene polymorphism at position −460, we used the polymerase chain reaction restriction fragment length polymorphism method. Serum levels of VEGF protein were measured using the ELISA test. The presence of the G allele (GA or GG) in the −1154 VEGF polymorphism was associated with an increased risk of BCC development (OR = 7.28, p < 0.0001). Furthermore, the carriers of the AA genotype in −1154 VEGF polymorphism showed significantly reduced risks of BCC (OR = 0.14, p < 0.0001). It was also shown that the GTC haplotype of VEGF predisposes to BCC development (OR = 1.69, p = 0.013), while the presence of the ATG haplotype significantly reduces this risk (OR = 0.17, p = 0.00001). We have found significantly increased VEGF serum levels among BCC patients, in comparison with the healthy controls (mean 596.7 ± 393.5 pg/ml; range 60.1–931.4 vs. 255.9 ± 174.6 pg/ml; range 42.2–553.0 pg/ml; p < 0.0004). The serum levels of VEGF significantly correlated with tumor size: r = 0.41, p < 0.0001. Our results testify to the importance of −1154 G/A VEGF gene polymorphisms in altering the risk of BCC among the population from northern Poland.