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. Impact: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.
Written by:
van Bemmel D, Lenz P, Liao LM, Baris D, Sternberg LR, Warner A, Johnson A, Jones M, Kida M, Schwenn M, Schned AR, Silverman DT, Rothman N, Moore LE Are you the author?
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 6120 Executive Blvd., EPS Rm. 8102, Bethesda, MD 20852.
Reference: Cancer Epidemiol Biomarkers Prev. 2012 Jul;21(7):1143-8
doi: 10.1158/1055-9965.EPI-11-1030
PubMed Abstract
PMID: 22539607