Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2015; 21(35): 10057-10061
Published online Sep 21, 2015. doi: 10.3748/wjg.v21.i35.10057
Stool DNA methylation assays in colorectal cancer screening
Tanya Kadiyska, Alexander Nossikoff
Tanya Kadiyska, Genetic Medico-Diagnostic Laboratory Genica, Sofia 1463, Bulgaria
Tanya Kadiyska, Department of Medical Chemistry and Biochemistry, Sofia Medical University, Sofia 1431, Bulgaria
Alexander Nossikoff, University Hospital Lozenets, Sofia 1407, Bulgaria
Author contributions: Kadiyska T and Nossikoff A contributed equally to this work; Kadiyska T gave the idea and wrote the genetics section; and Nossikoff A wrote the clinical section and edited the whole text.
Conflict-of-interest statement: Here with we declare that we have no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Tanya Kadiyska, PhD, Department of Medical Chemistry and Biochemistry, Sofia Medical University, 2 Zdrave str., Sofia 1431, Bulgaria. kadiyska_t@yahoo.com
Telephone: +359-2-9530715 Fax: +359-2-9530715
Received: January 18, 2015
Peer-review started: January 19, 2015
First decision: June 2, 2015
Revised: June 18, 2015
Accepted: August 25, 2015
Article in press: August 25, 2015
Published online: September 21, 2015
Abstract

Colorectal cancer (CRC) is fourth most common cancer in men and third in women worldwide. Developing a diagnostic panel of sensitive and specific biomarkers for the early detection of CRC is recognised as to be crucial for early initial diagnosis, which in turn leads to better long term survival. Most of the research on novel potential CRC biomarkers in the last 2 decades has been focussed on stool DNA analysis. In this paper, we describe the recent advances in non-invasive CRC screening and more specifically in molecular assays for aberrantly methylated BMP3 and NDRG4 promoter regions. In several research papers these markers showed superior rates for sensitivity and specificity in comparison to previously described assays. These tests detected the majority of adenomas ≥ 1 cm in size and the detection rates progressively increased with larger adenomas. The methylation status of the BMP3 and NDRG4 promoters demonstrated effective detection of neoplasms at all sites throughout the colon and was not affected by common clinical variables. Recently, a multitarget stool DNA test consisting of molecular assays for aberrantly methylated BMP3 and NDRG4 promoter regions, mutant KRAS and immunochemical assay for human haemoglobin has been made commercially available and is currently reimbursed in the United States. Although this is the most sensitive non-invasive CRC screening test, there is the need for further research in several areas - establishment of the best timeframe for repeated DNA stool testing; validation of the results in populations outside of North America; usefulness for surveillance and prognosis of patients; cost-effectiveness of DNA stool testing in real-life populations.

Keywords: Colorectal cancer, Screening programs, BMP3, NDRG4, Promoter hypermethylation

Core tip: Developing a diagnostic panel of sensitive and specific biomarkers for the early detection of colorectal cancer (CRC) is recognised as to be crucial for early initial diagnosis, which in turn leads to better long term survival. In this paper, we describe the recent advances in non-invasive CRC screening and more specifically in molecular assays for aberrantly methylated BMP3 and NDRG4 promoter regions. These markers show superior rates for sensitivity and specificity in comparison to previously described assays.