gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

Hypermethylation of sFRP1 Gene in Stool DNA Test: a Future Technology in Colorectal Cancer Screening

Meeting Abstract

  • corresponding author presenting/speaker W. Zhang - Chirurgische Klink FAU Erlangen-Nürnberg, Deutschland
  • M. Bauer - Chirurgische Klink FAU Erlangen-Nürnberg
  • M. Stürzl - Chirurgische Klink FAU Erlangen-Nürnberg
  • W. Hohenberger - Chirurgische Klink FAU Erlangen-Nürnberg
  • K. Matzel - Chirurgische Klink FAU Erlangen-Nürnberg

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO526

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dkk2006/06dkk636.shtml

Published: March 20, 2006

© 2006 Zhang et al.
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Outline

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Background: Stool DNA test is considered as a future technology in screening for colorectal cancer (CRC). Both genetic and epigenetic changes in shed cells from gastrointestinal tumours into stool could be detected. Epigenetic hypermethylation can result in transcriptional silencing of tumour suppressor genes and is considered to be a key event of sporadic colorectal carcinogenesis. sFRP1 is a tumour suppressor protein that contains a domain similar to one of WNT-receptor proteins and inhibits WNT-receptor binding to its signal transduction molecules. Detection of hypermethylation of sFRP1 gene in human DNA isolated from stools might provide a novel strategy for the detection of sporadic CRC. Our study aims to prove the methylation status of sFRP1 gene in stool samples, and compare the DNA methylation status before and after neoadjuvant radiochemotherapy.

Methods: To explore the feasibility of stool DNA test, fecal sampleswere obtained from 40 CRC patients (CRC patients post neoadjuvant radiochemotherapy n=10). Twenty fecal sampleswere obtained from patients without evidence of gastrointestinal disease or neoplasia. Isolated genomic DNA from stoolwas modified with sodium bisulfite and analyzed by specific PCR for methylation of sFRP1 promoter.

Results: With stool DNA test wewere able to detect the hypermethylation in the promoter region of sFRP1 gene in the fecal DNA from colorectal cancer patients (p=0.001). Sensitivity was 81%, specificity was 87%. Methylation status of sFRP1 gene was significantly changed after neoadjuvant radiochemotherapy (p=0.05).

Conclusion: The hypermethylation of sFRP1 gene in the stool DNA test has a high sensitivity and specificity for CRC and may be valuable for screening purposes, especial for the sporadic CRC. Compared with current colorectal cancer screening methods, stool DNA test is more patient-friendly, non-invasive, more sensitive and specific. The cost-effectiveness of screening may also be improved by using single DNA stool test with one sensitive DNA marker. The methylation status of sFRP1 seems to be changed after neoadjuvant radiochemotherapy, which may open new fieldsfor CRC research. Summarized this new diagnostic tool may yield benefits in earlier detection and in the design of better antitumour interventions.