Association of genetic variants in VEGF-A with clinical recurrence in prostate cancer patients treated with definitive radiotherapy.

background and purposeVascular endothelial growth factor-A (VEGF-A), a key regulator of tumor-induced angiogenesis, is critical for tumor growth and metastasization. The goal of the present study was to evaluate the prognostic value of VEGF single nucleotide polymorphisms (SNPs) and haplotypes for clinical recurrence after definitive radiotherapy for prostate cancer. PATIENTS AND

methodsThe association of seven VEGF-A polymorphisms and their haplotypes with clinical recurrence (defined as the occurrence of local recurrence and/or distant metastases) in 496 prostate cancer patients treated with definitive radiotherapy were investigated. Genotypes were determined by 5'-nuclease (TaqMan) assays; haplotypes were analyzed using the Haploview program.

resultsWithin a median follow-up time of 80 months, 44 patients (9 %) developed clinical recurrences. Haplotype analysis showed two separate blocks of high-linkage disequilibrium, formed by five polymorphisms (- 2578C > A, - 2489C > T, - 1498C > T, - 634G > C, - 7C > T) upstream of the coding sequence (CCCCC, ATTGC, CCCGC, ATTGT) and two polymorphisms (936C > T, 1612G > A) downstream of the coding sequence (CA, CG, TG). Carriers of at least 1 copy of the ATTGC haplotype were at higher risk of recurrence (hazard ratio [HR] 3.83; 95 %CI 1.48-9.90, p = 0.006); for carriers of 2 copies, the HR was 4.85 (95 %CI 1.72-13.6; p = 0.003). In multivariate analysis, patients harboring at least one copy of the ATTGC haplotype remained at increased risk of recurrence (HR 3.63, 95 %CI 1.38-9.55, p = 0.009); in patients carrying 2 copies, the HR was 4.72 (95 %CI 1.64-13.6, p = 0.004).

conclusionOur findings indicate that the VEGF-A ATTGC haplotype may predict clinical recurrence in prostate cancer patients treated with radiotherapy.