title: Post-treatment recovery of suboptimal DNA repair capacity and gene expression levels in colorectal cancer patients.
abstract: DNA repair in blood cells was observed to be suboptimal in cancer patients at diagnosis, including colorectal cancer (CRC). To explore the causality of this phenomenon, we studied the dynamics of DNA repair from diagnosis to 1 yr follow-up, and with respect to CRC treatment. Systemic CRC therapy is targeted to DNA damage induction and DNA repair is thus of interest. CRC patients were blood-sampled three times in 6-mo intervals, starting at the diagnosis, and compared to healthy controls. DNA repair was characterized by mRNA levels of 40 repair genes, by capacity of nucleotide excision repair (NER), and by levels of DNA strand breaks (SBs). NER and base excision repair genes were significantly under-expressed (P < 0.016) in patients at diagnosis compared to controls, in accordance with reduced NER function (P = 0.008) and increased SBs (P = 0.015). Six months later, there was an increase of NER capacity, but not of gene expression levels, in treated patients only. A year from diagnosis, gene expression profiles and NER capacity were significantly modified in all patients and were no longer different from those measured in controls. All patients were free of relapse at the last sampling, so we were unable to clarify the impact of DNA repair parameters on treatment response. However, we identified a panel of blood DNA repair-related markers discerning acute stage of the disease from the remission period. In conclusion, our results support a model in which DNA repair is altered as a result of cancer.
authors.affiliation: Institute of Experimental Medicine, ASCR, Prague, Czech Republic.|First Faculty of Medicine, Institute of Biology and Medical Genetics, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Slyskova
authors.affiliation: University of Torino, Torino, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cordero
authors.affiliation: Human Genetics Foundation (HuGeF), Torino, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pardini
authors.affiliation: Institute of Biotechnology, ASCR, Prague, Czech Republic.
authors.forename: Vlasta
authors.initials: V
authors.lastname: Korenkova
authors.affiliation: Institute of Experimental Medicine, ASCR, Prague, Czech Republic.|First Faculty of Medicine, Institute of Biology and Medical Genetics, Prague, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Vymetalkova
authors.affiliation: Institute of Experimental Medicine, ASCR, Prague, Czech Republic.|First Faculty of Medicine, Institute of Biology and Medical Genetics, Prague, Czech Republic.|Faculty of Science, Charles University, Prague, Czech Republic.
authors.forename: Ludovit
authors.initials: L
authors.lastname: Bielik
authors.affiliation: Institute of Experimental Medicine, ASCR, Prague, Czech Republic.|First Faculty of Medicine, Institute of Biology and Medical Genetics, Prague, Czech Republic.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Vodickova
authors.affiliation: Biomedical Centre, Medical School Pilsen, Charles University in Prague, Pilsen, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Pitule
authors.affiliation: Biomedical Centre, Medical School Pilsen, Charles University in Prague, Pilsen, Czech Republic.|Clinic of Oncology and Radiotherapy, Faculty Hospital in Pilsen, Charles University, Pilsen, Czech Republic.
authors.forename: Vaclav
authors.initials: V
authors.lastname: Liska
authors.affiliation: Clinic of Oncology and Radiotherapy, Faculty Hospital in Pilsen, Charles University, Pilsen, Czech Republic.
authors.forename: Vit Martin
authors.initials: VM
authors.lastname: Matejka
authors.affiliation: Thomayer Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Levy
authors.affiliation: Thomayer Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Buchler
authors.affiliation: Institute of Biotechnology, ASCR, Prague, Czech Republic.|TATAA Biocenter, Goteborg, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Kubista
authors.affiliation: Institute of Experimental Medicine, ASCR, Prague, Czech Republic.|Human Genetics Foundation (HuGeF), Torino, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Naccarati
authors.affiliation: Institute of Experimental Medicine, ASCR, Prague, Czech Republic.|First Faculty of Medicine, Institute of Biology and Medical Genetics, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Vodicka
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D053960:DNA Breaks / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D012007:Rectum / Q000187:drug effects / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents
keywords: Colorectal cancer; DNA instability; DNA repair; anti-cancer therapy; biomarker; follow-up study