Identify DNA methylation markers suitable for sensitive and specific plasma-based detection of advanced colorectal adenomas.
ID
Source
Brief title
Condition
- Benign neoplasms gastrointestinal
- Gastrointestinal neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Difference in DNA methylation of a certain adenoma subtype and normal mucosa of
controls.
Difference in cfDNA methylation of screening colonoscopy patients with advanced
adenoma and those found to be free of colorectal polyps/cancer and
inflammation. .
Secondary outcome
Difference in DNA methylation of a certain adenoma subtype and leucocytes of
controls, (pre)malignant tissue from cancer other than CRC or inflammatory
conditions, or non-advanced polyps.
Difference in cfDNA methylation of screening colonoscopy patients with advanced
adenoma and those with non-advanced polyps.
Background summary
Prevention of colorectal cancer (CRC) by screening rests on effective detection
and colonoscopic removal of advanced precursor lesions (adenomas).
Unfortunately, the Fecal Occult Blood Test (FOBT) used in the Dutch CRC
screening program as triage test for colonoscopy, only detects 27% of advanced
conventional adenomas. Furthermore, it has become increasingly apparent in
recent years that approximately 1/3 of CRCs arise from sessile serrated
adenomas/polyps (SSA/Ps). Recently, it has been shown that fecal occult blood
testing has no value in SSA/P detection due to their largely non-hemorrhagic
nature. Obviously, the identification of sensitive and specific biomarkers for
advanced precursor lesions, including SSA/Ps, is fundamental to reduce the risk
of CRC.
Hypermethylated genes are attractive candidate biomarkers as cancer-specific
methylation occurs early in tumorigenesis. Hypermethylation of cytosine
residues in CpG islands, which occur in the promoter regions of many genes, may
disrupt function by reducing or silencing transcription and represents a key
mechanism for inactivation of tumor suppressor genes.The demonstration of
significantly different methylation frequencies of specific genes between early
and advanced adenomas, suggests these genes have the potential to be used as
biomarkers that can distinguish between clinically insignificant and
screen-relevant precursor lesions. Recently, it has been shown that 54% of
patients with advanced conventional or serrated adenoma can be detected by
fecal DNA testing, which largely relies on hypermethylation analysis.
Differentiation of adenoma patients from controls by measuring hypermethylation
of circulating free DNA (cfDNA), isolated from plasma or serum, has also been
demonstrated. Advantages of cfDNA testing include more convenient and
acceptable sampling, easier sample processing and absence of interfering
microflora. Until now, hypermethylation has only rarely been evaluated in
patients with SSA/Ps and, additionally, current candidate cfDNA methylation
markers detect conventional adenomas with insufficient sensitivity. To improve
screening performance for SSA/Ps and advanced conventional adenomas by means of
cfDNA testing, systematic identification of the most informative CpG sites is
required.
Study objective
Identify DNA methylation markers suitable for sensitive and specific
plasma-based detection of advanced colorectal adenomas.
Study design
cross-sectional study
Study burden and risks
A single blood sample of 10cc will be drawn by way of an infusion needle
(already present) and from colonoscopy-negative patients four biopsies of
normal mucosa will be taken. The burden associated with participation is
minimal, since these samples will be collected during a colonoscopy procedure
performed within the scope of patients* medical treatment. Moreover, biopsy
taking during colonoscopy is routinely performed and considered an in general
safe procedure. In case the patient receives a subsequent endoscopy to check
completeness of polypectomy an additional blood sample of 10 cc may be drawn by
way of an infusion needle. In case the patient visits the outpatient clinic in
connection with the screening colonoscopy an additional blood sample of 10 cc
may be drawn by venipuncture. This may cause a bruise.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
- >45 years
- scheduled for screening colonoscopy or subsequent polypectomy. Indications for screening colonoscopy are rectal blood loss, anemia, change in bowel habits, positive iFOBT or positive family history of adenomas or CRC (two or more first degree relatives or one or more at age 50 years or less).
Exclusion criteria
- having hereditary colorectal cancer syndrome (e.g. Lynch syndrome or polyposis syndromes) or suspicion thereof
- having inflammatory bowel disease
- previous adenoma
- cancer within the past five years
- colonoscopy that is incomplete or associated with a poor preparation
- lack of histological classification of polyps removed at screening colonoscopy
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL49428.041.14 |