DNA methylation patterns in blood of patients with colorectal cancer and adenomatous colorectal polyps

Int J Cancer. 2012 Sep 1;131(5):1153-7. doi: 10.1002/ijc.26484. Epub 2011 Nov 19.


Colorectal cancer (CRC) screening rates are currently suboptimal. Blood-based screening could improve rates of earlier detection for CRC and adenomatous colorectal polyps. In this study, we evaluated the feasibility of plasma-based detection of early CRC and adenomatous polyps using array-mediated analysis methylation profiling of 56 genes implicated in carcinogenesis. Methylation of 56 genes in patients with Stages I and II CRC (N=30) and those with adenomatous polyps (N=30) were compared with individuals who underwent colonoscopy and were found to have neither adenomatous changes nor CRC. Composite biomarkers were developed for adenomatous polyps and CRC, and their sensitivity and specificity was estimated using five-fold cross validation. Six promoters (CYCD2, HIC1, PAX 5, RASSF1A, RB1 and SRBC) were selected for the biomarker, which differentiated CRC patients and controls with 84% sensitivity and 68% specificity. Three promoters (HIC1, MDG1 and RASSF1A) were selected for the biomarker, which differentiated patients with adenomatous polyps and controls with sensitivity of 55% and specificity of 65%. Methylation profiling of plasma DNA can detect early CRC with significant accuracy and shows promise as a methodology to develop biomarkers for CRC screening.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoma / blood
  • Adenoma / diagnosis*
  • Adenoma / genetics
  • Adenomatous Polyps / blood
  • Adenomatous Polyps / diagnosis*
  • Adenomatous Polyps / genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Colon / metabolism
  • Colon / pathology
  • Colonic Polyps / blood
  • Colonic Polyps / diagnosis*
  • Colonic Polyps / genetics
  • Colonoscopy
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / genetics
  • DNA Methylation*
  • Early Detection of Cancer
  • Female
  • Humans
  • Male
  • Mass Screening
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Rectum / metabolism
  • Rectum / pathology
  • Sensitivity and Specificity


  • Biomarkers, Tumor