title: Concordance of genotype for polymorphisms in DNA isolated from peripheral blood and colorectal cancer tumor samples.
abstract: OBJECTIVE
  Results from different pharmacogenetic association studies in colorectal cancer are often conflicting. Both peripheral blood and formalin-fixed, paraffin-embedded (FFPE) tissue are routinely used as DNA source. This could cause bias due to somatic alterations in tumor tissue, such as loss of heterozygosity. We therefore compared genotypes in DNA from peripheral blood and FFPE colorectal tumor samples for SNPs with putative influence on the cytotoxicity of chemotherapy.
  
  
  METHODS
  Eleven SNPs in nine genes involved in anticancer drug metabolism or efficacy were determined in matched samples from blood and FFPE tissue of colorectal tumors by pyrosequencing and TaqMan(®) techniques. The κ-statistic was calculated to assess concordance.
  
  
  RESULTS
  A total of 149 paired FFPE tissue and EDTA blood DNA samples were available for comparison. Overall, 20 out of 1418 genotypes were discordant (1.4%); in ten cases, loss of heterozygosity could not be ruled out. Only GSTP1 showed significant discordance between FFPE tissue and blood genotype (κ = 0.947; 95% CI: 0.896-0.998).
  
  
  CONCLUSIONS
  FFPE tissue-derived DNA can be used as a valid proxy for germline DNA for a selection of SNPs in (retrospective) pharmacogenetic association studies in colorectal cancer. However, for future studies, genotyping of blood-derived DNA is preferred.
authors.affiliation: Department of Clinical Oncology (K-1-P), Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Lieke
authors.initials: L
authors.lastname: van Huis-Tanja
authors.forename: Dinemarie
authors.initials: D
authors.lastname: Kweekel
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.forename: Miriam
authors.initials: M
authors.lastname: Koopman
authors.forename: Kees
authors.initials: K
authors.lastname: Punt
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Guchelaar
authors.forename: Tahar
authors.initials: T
authors.lastname: van der Straaten
mesh_terms: D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics* / Q000473:pathology; D005557:Formaldehyde; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D019656:Loss of Heterozygosity / Q000235:genetics; D016612:Paraffin Embedding; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012189:Retrospective Studies; D016707:Tissue Fixation
chemical_list: D005557:Formaldehyde