title: Functional, genetic, and epigenetic aspects of base and nucleotide excision repair in colorectal carcinomas.
abstract: OBJECTIVE
  DNA repair capacity (DRC) is a determinant not only of cancer development but also of individual response to therapy. Previously, altered base and nucleotide excision repair (BER and NER) have been described in lymphocytes of patients with sporadic colorectal cancer. We, for the first time, evaluate both excision repair capacities in human colon biopsies to study their participation in colorectal tumorigenesis.
  
  
  METHODS
  Seventy pairs of tumor and adjacent healthy tissues were analyzed for BER- and NER-specific DRC by a comet repair assay. Tissue pairs were further compared for expression levels of a panel of 25 BER and NER genes complemented by their promoter methylation status.
  
  
  RESULTS
  We observed a moderate increase of NER-DRC (P = 0.019), but not of BER-DRC in tumors. There was a strong correlation between both tissues for all investigated parameters (P < 0.001). However, 4 NER (CSB, CCNH, XPA, XPD) and 4 BER (NEIL1, APEX1, OGG1, PARP1) genes showed a 1.08- to 1.28-fold change difference in expression in tumors (P < 0.05). Individual gene expression levels did not correlate with overall DRC, and we did not detect any aberrant methylation of the investigated genes.
  
  
  CONCLUSIONS
  Our complex analysis showed that tumor cells are not deficient in BER and NER, but rather follow patterns characteristic for each individual and are comparable with adjacent tissue. Alteration of excision repair pathways is not a pronounced event in colorectal carcinogenesis. This study shows the feasibility of DRC evaluation in human solid tissues, representing a complex marker of multigene DNA repair processes.
authors.affiliation: Institute of Experimental Medicine, and Institute of Biotechnology, Academy of Sciences, Czech Republic. j.slyskova@gmail.com
authors.forename: Jana
authors.initials: J
authors.lastname: Slyskova
authors.forename: Vlasta
authors.initials: V
authors.lastname: Korenkova
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Collins
authors.forename: Pavel
authors.initials: P
authors.lastname: Prochazka
authors.forename: Ludmila
authors.initials: L
authors.lastname: Vodickova
authors.forename: Jiri
authors.initials: J
authors.lastname: Svec
authors.forename: Ludmila
authors.initials: L
authors.lastname: Lipska
authors.forename: Miroslav
authors.initials: M
authors.lastname: Levy
authors.forename: Michaela
authors.initials: M
authors.lastname: Schneiderova
authors.forename: Vaclav
authors.initials: V
authors.lastname: Liska
authors.forename: Lubos
authors.initials: L
authors.lastname: Holubec
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.forename: Pavel
authors.initials: P
authors.lastname: Soucek
authors.forename: Alessio
authors.initials: A
authors.lastname: Naccarati
authors.forename: Pavel
authors.initials: P
authors.lastname: Vodicka
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D004260:DNA Repair; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic