Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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
Web of Science
PubMed
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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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- Abstract:
- 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)
- Radiotherapy
- Prostate cancer
- Late toxicity
- Death receptor pathway
- FAS, FASL polymorphisms