The –553 T/A polymorphism in the promoter region of the FGF2 gene is associated with increased breast cancer risk in Polish women

INTRODUCTION Fibroblast growth factor-2 (FGF2) is an important signalling molecule contributing to angiogenesis, tumour growth and progression and its expression is implicated in breast cancer (BC) development. We investigated whether -553 T/A FGF2 gene polymorphism is associated with the risk and progression of BC in Polish women. MATERIAL AND METHODS The -553 T/A polymorphism was genotyped in 230 breast cancer patients and 245 control subjects, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. Moreover, FastQuant human angiogenesis array was used to measure FGF2 levels in tumour (n = 127) and serum (n = 76) samples. RESULTS The T/A genotypes (OR = 2.12, 95% CI: 1.20-3.74) (p = 0.08) and the combined heterozygotes T/A and homozygote A/A (OR = 2.18, 95% CI: 1.24-3.83) (p = 0.006) had an increased risk of BC. The median FGF2 levels in the tumours of A allele carriers were significantly increased compared to T/T patients, whereas in serum FGF2 levels were hardly altered among different genotype carriers. Significantly higher frequency of A allele was found in patients with lymph node metastases (OR = 2.53; 95% CI: 1.23-5.17) (p = 0.009) and human epidermal growth factor receptor 2 positive tumour (OR = 3.22, 95% CI: 1.49-6.99) (p = 0.002). Furthermore, Kaplan-Meier survival analysis showed that the A allele predicted worse disease-free survival (DFS) in BC patients. CONCLUSIONS Our study shows for the first time that the -553 T/A FGF2 gene polymorphism may be associated with a risk of BC developing and progression in Polish women and may have prognostic value for the assessment of BC high-risk groups.