Non-invasive markers for colorectal cancer screening.

Rationale: Colonoscopy is considered to be the gold standard for the detection of colorectal neoplasia. However, this method has important disadvantages, such as invasiveness, complication risk, and possible shortage of clinical capacity. Therefore, the potential additional role of non-invasive screening methods as pre-selection tool for colonoscopy, deserves further investigation. Non-invasive markers for CRC have recently been developed for blood and feces. These markers are currently tested in an average-risk population. In patients at high-risk, as a result of a positive family history, the clinical utility of these markers as pre-selection tool has not been investigated yet. Likewise, no data are available regarding the potential role of these markers in risk stratification of these patients. The clinical utility of such markers to identify risk profiles and hence, to design more individualized surveillance strategies, deserves further investigation.



Objective:

Two issues will be addressed:

I. To study the diagnostic accuracy of molecular and protein markers in screening for colorectal neoplasia in subjects at high-risk for CRC and CRC patients, in comparison with average-risk subjects.

II. To investigate the role of non-invasive markers in risk stratification of patients at high-risk for CRC. To provide insights in the molecular features of patients at high-risk.



Study design:

For this purpose, a prospective, cross-sectional study will be performed. The following groups of patients will be included:

i) 200 patients with a family history of CRC and

ii) 150 patients diagnosed with CRC.
Medical data will be collected, all subjects will undergo colonoscopy and non-invasive markers for colorectal neoplasia will be investigated in blood and fecal samples. Additionally, a subset of patients with a non-colorectal gastrointestinal malignancy (e.g. esophageal, gastric or pancreatic cancer) will be included in order to investigate the influence of these lesions on the non-invasive markers profile.

Non-invasive markers have an additional role in screening and surveillance of patients at high risk for CRC.

2 years

Collection of blood and fecal samples (once). Non-invasive markers for colorectal neoplasia will be determined in blood, feces and tissue. All combinations of markers will be tested in order to optimize the diagnostic accuracy for colorectal neoplasia, considering the outcome of colonoscopy as the gold standard. In addition the results of the non-invasive markers in patients at high-risk will be compared with the results of an average-risk population, in order to identify risk factors.