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Langsenlehner, T; Thurner, EM; Renner, W; Gerger, A; Kapp, KS; Langsenlehner, U.
Association of genetic variants in VEGF-A with clinical recurrence in prostate cancer patients treated with definitive radiotherapy.
Strahlenther Onkol. 2014; 190(4):364-369
Doi: 10.1007/s00066-013-0503-2
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
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Langsenlehner Tanja
- Co-Autor*innen der Med Uni Graz
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Gerger Armin
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Kapp Karin S.
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Langsenlehner Uwe
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Renner Wilfried
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Thurner Eva-Maria
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- Abstract:
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Vascular 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.
The 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.
Within 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).
Our findings indicate that the VEGF-A ATTGC haplotype may predict clinical recurrence in prostate cancer patients treated with radiotherapy.
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Aged -
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Aged, 80 and over -
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Aged, 80 and over - epidemiology
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Disease-Free Survival -
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Genetic Association Studies -
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Genetic Predisposition to Disease - epidemiology
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Genetic Predisposition to Disease - genetics
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Genetic Variation - genetics
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Heterozygote -
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Humans -
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Longitudinal Studies -
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Male -
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Middle Aged -
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Neoplasm Recurrence, Local - genetics
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Neoplasm Recurrence, Local - mortality
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Neoplasm Recurrence, Local - radiotherapy
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Polymorphism, Single Nucleotide - genetics
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Prevalence -
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Prostatic Neoplasms - genetics
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Prostatic Neoplasms - mortality
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Prostatic Neoplasms - radiotherapy
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Risk Factors -
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Survival Rate -
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Vascular Endothelial Growth Factor A - genetics
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Prostate neoplasms
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Neoplasm recurrence, local
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Prognosis
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Vascular endothelial growth factor-A
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Genotypes