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Post‐treatment recovery of suboptimal DNA repair capacity and gene expression levels in colorectal cancer patients
Author(s) -
Slyskova Jana,
Cordero Francesca,
Pardini Barbara,
Korenkova Vlasta,
Vymetalkova Veronika,
Bielik Ludovit,
Vodickova Ludmila,
Pitule Pavel,
Liska Vaclav,
Matejka Vit Martin,
Levy Miroslav,
Buchler Tomas,
Kubista Mikael,
Naccarati Alessio,
Vodicka Pavel
Publication year - 2015
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22141
Subject(s) - dna repair , biology , colorectal cancer , base excision repair , cancer , gene , nucleotide excision repair , dna damage , dna mismatch repair , dna , cancer research , gene expression , microbiology and biotechnology , medicine , genetics
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. © 2014 Wiley Periodicals, Inc.