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In vitro radiation‐induced expression of XPC mRNA as a possible biomarker for developing adverse reactions during radiotherapy
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| Zeitschriftentitel: | International Journal of Cancer |
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| Personen und Körperschaften: | , , , , , , , |
| In: | International Journal of Cancer, 121, 2007, 10, S. 2340-2345 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
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| Schlagwörter: |
| Zusammenfassung: | <jats:title>Abstract</jats:title><jats:p>Repair of radiation‐induced DNA damage is believed to play a critical role in developing adverse reactions during radiotherapy. Ionizing radiation induces transcription of several DNA repair genes including <jats:italic>XPC</jats:italic> as a part of the p53‐transmitted stress response. <jats:italic>XPC</jats:italic> gene induction was measured to analyze whether it predicts occurrence of therapy‐related acute side effects. Prostate cancer patients (<jats:italic>n</jats:italic> = 406) receiving radiotherapy were monitored for development of acute adverse effects using common toxicity criteria. For gene induction analysis, lymphocytes from 99 patients were selected according to their observed grade of clinical side effects. Cells were irradiated <jats:italic>in vitro</jats:italic> with 5 Gy and analyzed after 4 hr for <jats:italic>XPC</jats:italic> gene induction using reverse transcription and quantitative real‐time PCR. Analysis of modulation of <jats:italic>XPC</jats:italic> induction by personal, clinical or lifestyle factors was included. Inter‐individual induction of <jats:italic>XPC</jats:italic> expression by ionizing radiation varied up to 20‐fold (0.29–5.77) and was significantly higher in current or exsmokers than in never‐smokers (<jats:italic>p</jats:italic> value: 0.008). Patients with <jats:italic>XPC</jats:italic> induction above the 90th percentile compared to those with lower induction levels were at increased risk of suffering from adverse reactions during radiotherapy (odds ratio 5.3, 95% confidence interval 1.2–24.5; adjusted for smoking). In summary, <jats:italic>XPC</jats:italic> mRNA levels induced by ionizing radiation were shown for the first time to be strongly affected by smoking and to be associated with an approximately 5‐fold increased risk for developing acute side effects of radiotherapy. The predictive value of DNA damage‐induced <jats:italic>XPC</jats:italic> levels as a possible biomarker for radiosensitivity has to be further investigated. © 2007 Wiley‐Liss, Inc.</jats:p> |
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| Umfang: | 2340-2345 |
| ISSN: |
0020-7136
1097-0215 |
| DOI: | 10.1002/ijc.22981 |