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.
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.
Authors: Mashaal Dhir; Shinichi Yachida; Leander Van Neste; Sabine C Glöckner; Jana Jeschke; Emmanouil P Pappou; Elizabeth A Montgomery; James G Herman; Stephen B Baylin; Christine Iacobuzio-Donahue; Nita Ahuja Journal: Int J Cancer Date: 2011-03-11 Impact factor: 7.396
Authors: Sabine C Glöckner; Mashaal Dhir; Joo Mi Yi; Kelly E McGarvey; Leander Van Neste; Joost Louwagie; Timothy A Chan; Wolfram Kleeberger; Adriaan P de Bruïne; Kim M Smits; Carolina A J Khalid-de Bakker; Daisy M A E Jonkers; Reinhold W Stockbrügger; Gerrit A Meijer; Frank A Oort; Christine Iacobuzio-Donahue; Katja Bierau; James G Herman; Stephen B Baylin; Manon Van Engeland; Kornel E Schuebel; Nita Ahuja Journal: Cancer Res Date: 2009-05-12 Impact factor: 12.701
Authors: Mashaal Dhir; Elizabeth A Montgomery; Sabine C Glöckner; Kornel E Schuebel; Craig M Hooker; James G Herman; Stephen B Baylin; Susan L Gearhart; Nita Ahuja Journal: J Gastrointest Surg Date: 2008-08-21 Impact factor: 3.452