DNA stool test for colorectal cancer: hypermethylation of the secreted frizzled-related protein-1 gene

Dis Colon Rectum. 2007 Oct;50(10):1618-26; discussion 1626-7. doi: 10.1007/s10350-007-0286-6.

Abstract

Purpose: To investigate a potential mode of noninvasive screening for colorectal cancer, we evaluated the hypermethylation of the secreted frizzled-related protein-1 gene promoter in human stool DNA.

Methods: In stool samples from 36 patients with colorectal neoplasia (7 adenoma, 29 colorectal cancer) and 17 healthy control subjects, isolated DNA was treated with sodium bisulfite and analyzed by methylation-specific polymerase chain reaction with primers specific for methylated or unmethylated promoter sequences of the secreted frizzled-related protein-1 gene.

Results: Hypermethylation of the secreted frizzled-related protein-1 promoter was present in the stool DNA of patients with adenoma and colorectal cancer. A sensitivity of 89 percent and specificity of 86 percent were achieved in the detection of colorectal neoplasia. The difference in hypermethylation status of the secreted frizzled-related protein-1 promoter between the patients with colorectal neoplasia and the control group was statistically highly significant (P < 0.001). Adenoma and early tumor Stage I (International Union Against Cancer) displayed both unmethylated and methylated secreted frizzled-related protein-1 promoter sequences, whereas advanced tumor stages showed only methylated secreted frizzled-related protein-1 (P = 0.05).

Conclusions: The results indicate that this DNA stool test of hypermethylation of the secreted frizzled-related protein-1 promoter is a sensitive and specific method. It has the potential of a clinically useful test for the early detection of colorectal cancer.

MeSH terms

  • Adenoma / diagnosis
  • Adenoma / genetics
  • Adenoma / metabolism*
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma / diagnosis
  • Carcinoma / genetics
  • Carcinoma / metabolism*
  • Case-Control Studies
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • DNA Methylation*
  • Feasibility Studies
  • Feces*
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic / physiology

Substances

  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • SFRP1 protein, human