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Thurner, EM; Krenn-Pilko, S; Langsenlehner, U; Renner, W; Gerger, A; Kapp, KS; Langsenlehner, T.
Association of genetic variants in apoptosis genes FAS and FASL with radiation-induced late toxicity after prostate cancer radiotherapy.
Strahlenther Onkol. 2014; 190(3):304-309 Doi: 10.1007/s00066-013-0485-0
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Führende Autor*innen der Med Uni Graz
Langsenlehner Tanja
Thurner Eva-Maria
Co-Autor*innen der Med Uni Graz
Gerger Armin
Kapp Karin S.
Krenn-Pilko Sabine
Langsenlehner Uwe
Renner Wilfried

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Fas ligand (FASL) triggers apoptotic cell death by cross-linking with its receptor FAS, and after irradiation, expression of FAS and FASL is increased. In the present study, we investigated the association between common polymorphisms in the genes for FAS and FASL and the risk of late side effects after radiotherapy for prostate cancer. The role of FAS (- 1377G > A, rs2234767 and - 670A > G, rs1800682) and FASL (- 844C > T, rs763110) gene polymorphisms in the development of high-grade late rectal and/or urinary toxicity (defined as late toxicity EORTC/RTOG grade ≥ 2) was analyzed in 607 prostate cancer patients treated with radiotherapy. DNA was isolated and the selected polymorphisms were determined by 5'-nuclease (TaqMan) assays. After a median follow-up time of 82 months, high-grade late rectal and/or urinary toxicity was observed in 175 patients (29.7 %). Univariate analysis revealed a significantly decreased risk of high-grade late toxicity in carriers of the FASL - 844T allele. After adjusting for covariates, patients harboring at least one - 844T allele (CT or TT genotype) remained at decreased risk of high-grade late toxicity compared with patients harboring the CC genotype [hazard ratio (HR) 0.585, 95 %CI 0.39-0.878; p = 0.010]. For patients with the - 844TT genotype, the HR was 0.404 (95 %CI 0.171-0.956; p = 0.039) in multivariate analysis. No significant associations were found for the remaining polymorphisms analyzed. These results provide the first evidence that the presence of the FASL - 844T variant allele may have a protective effect against the development of high-grade late rectal and/or urinary side effects after prostate cancer radiotherapy.
Find related publications in this database (using NLM MeSH Indexing)
Aged -
Alleles -
Apoptosis - genetics
Combined Modality Therapy -
Cross-Sectional Studies -
Dose Fractionation, Radiation -
Fas Ligand Protein - genetics
Follow-Up Studies -
Gene Expression Regulation, Neoplastic - radiation effects
Genetic Predisposition to Disease - genetics
Genetic Variation - genetics
Humans -
Male -
Middle Aged -
Neoplasm Staging -
Organs at Risk -
Polymorphism, Genetic - genetics
Prostatectomy -
Prostatic Neoplasms - genetics
Prostatic Neoplasms - pathology
Prostatic Neoplasms - radiotherapy
Prostatic Neoplasms - surgery
Radiation Injuries - genetics
Radiotherapy Planning, Computer-Assisted -
Radiotherapy, Adjuvant -
Rectum - radiation effects
Risk Factors -
Urinary Bladder - radiation effects
fas Receptor - genetics

Find related publications in this database (Keywords)
Prostate cancer
Late toxicity
Death receptor pathway
FAS, FASL polymorphisms
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