In vitro radiation-induced expression of XPC mRNA as a possible biomarker for developing adverse reactions during radiotherapy.
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 XPC as a part of the p53-transmitted stress response. XPC gene induction was measured to analyze whether it predicts occurrence of therapy-related acute side effects. Prostate cancer patients (n = 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 in vitro with 5 Gy and analyzed after 4 hr for XPC gene induction using reverse transcription and quantitative real-time PCR. Analysis of modulation of XPC induction by personal, clinical or lifestyle factors was included. Inter-individual induction of XPC 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 (p value: 0.008). Patients with XPC 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, XPC 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 XPC levels as a possible biomarker for radiosensitivity has to be further investigated.
Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Katrin
K
Wiebalk
Peter
P
Schmezer
Silke
S
Kropp
Jenny
J
Chang-Claude
Oktay
O
Celebi
Jürgen
J
Debus
Helmut
H
Bartsch
Odilia
O
Popanda
D000368:Aged; D015415:Biomarkers; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D012333:RNA, Messenger / Q000235:genetics; D012907:Smoking; D015533:Transcriptional Activation
D015415:Biomarkers; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C086984:XPC protein, human