title: Correlation of LINE-1 methylation levels in patient-matched buffy coat, serum, buccal cell, and bladder tumor tissue DNA samples.
abstract: BACKGROUND
  Evidence suggests that global methylation levels in blood cell DNA may be a biomarker for cancer risk. To date, most studies have used genomic DNA isolated from blood or urine as a surrogate marker of global DNA methylation levels in bladder tumor tissue.
  
  
  METHODS
  A subset of 50 bladder cancer cases was selected from the New England Bladder Cancer Case-Control Study. Genomic DNA was isolated from buffy coat, buccal cells, serum, and formalin-fixed, paraffin-embedded tissue for each participant. DNA methylation at four CpG sites within the long interspersed nucleotide element (LINE-1) repetitive element was quantified using pyrosequencing and expressed as a mean methylation level across sites.
  
  
  RESULTS
  Overall, the mean percent (%) LINE-1 5-methylcytosine (%5MeC) level was highest in serum (80.47% ± 1.44%) and lowest in bladder tumor DNA (61.36% ± 12.74%) and levels varied significantly across tissue types (P = 0.001). An inverse association between LINE-1 mean %5MeC and tumor stage (P = 0.001) and grade (P = 0.002) was observed. A moderate correlation between patient-matched serum and buffy coat DNA LINE-1 %5MeC levels was found (r = 0.32, P = 0.03) but levels were uncorrelated among other matched genomic DNA samples.
  
  
  CONCLUSIONS
  The mean promoter LINE-1 %5MeC measurements were correlated between buffy coat and serum DNA samples. No correlation was observed between genomic DNA sources and tumor tissues; however a significant inverse association between tumor percent LINE-1 methylation and tumor stage/grade was found.
  
  
  CONCLUSIONS
  LINE-1 methylation measured in case blood DNA did not reflect that observed in bladder tumor tissue but may represent other factors associated with carcinogenesis.
authors.affiliation: Occupational and Environmental Epidemiology Branch, Epidemiology and Biostatistics Program, National Cancer Institute, NIH, DHHS, Bethesda, MD 20852, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: van Bemmel
authors.forename: Petra
authors.initials: P
authors.lastname: Lenz
authors.forename: Linda M
authors.initials: LM
authors.lastname: Liao
authors.forename: Dalsu
authors.initials: D
authors.lastname: Baris
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Sternberg
authors.forename: Andrew
authors.initials: A
authors.lastname: Warner
authors.forename: Alison
authors.initials: A
authors.lastname: Johnson
authors.forename: Michael
authors.initials: M
authors.lastname: Jones
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kida
authors.forename: Molly
authors.initials: M
authors.lastname: Schwenn
authors.forename: Alan R
authors.initials: AR
authors.lastname: Schned
authors.forename: Debra T
authors.initials: DT
authors.lastname: Silverman
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Lee E
authors.initials: LE
authors.lastname: Moore
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001773:Blood Cells / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism* / Q000473:pathology; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D015996:Survival Rate; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality
chemical_list: D014408:Biomarkers, Tumor; D004247:DNA