Validation of an Alternative Biological Test to Increase the Detection Sensitivity of a Colon Tumour
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Study type: Observational

Summary: 
      Screening campaigns for colorectal cancer (CRC) involve two steps: the detection of occult
      blood in stools using a Hemoccult GAIAC test (FOBT) on three consecutive stool samples,
      followed by colonoscopy if the result is positive. The information quality of the Hemoccult
      test, however, is poor: in the asymptomatic 50 to 74 year-old population, the detection
      sensitivity of polyps more than 1 cm in diameter is of the order of 10 to 30% and is 35 to
      50% for detecting colorectal cancers; specificity is 94 to 98% that of a complete
      colonoscopy. The I-FOBTs based on immunological detection and quantification of occult blood
      in stools are currently being evaluated; based on the threshold it can be more sensitive than
      FOBT, but enhances useless colonoscopies. Alternatively, with highest threshold of blood in
      stools, it may become highly specific and miss less advanced polyps. Faecal molecular tests
      based on the detection of human DNA anomalies (point gene mutations, methylation disorders of
      CG islets) appear to be more sensitive than the detection of occult blood in stools with no
      loss of specificity, but they are very expensive, thereby limiting their generalisation to
      the scale of population screening. A formal methylated DNA test has been validated in stools
      as well as in blood in a cohort of symptomatic individuals having undergone colonoscopy. The
      aim of the present study is to validate this test by taking advantage of the biotechnical
      expertise from renowned academic research teams and mass screening organisation.
    

Detailed description: 
      This study search to validate a test by taking advantage of the biotechnical expertise from
      renowned academic research teams and mass screening organisation.

      In order to reduce the cost of the present study the investigators will select in this
      preliminary study only those individuals who have a FOBT. However, we'll measure the blood
      level by using a I-FOBT test to quantify Haemoglobin concentration in stools. Furthermore,
      we'll use stool DNA to characterize microbiota according to the colonoscopy findings. In
      addition, the investigators believe it is important to include in the project, the creation
      of biological blood and urine collections from individuals having undergone both faecal tests
      and a reference colonoscopy. In the future, these collections will be made available to the
      national or international scientific community (after consent by the principal investigators)
      to validate any other molecular and/or protein marker including proteomic analysis by using
      MSS. The investigators will perform methylated DNA test in either stools or blood and will
      compare results to those of I-FOBT and colonoscopy.

      A simplified molecular test based on a combination of the search for methylation anomalies
      (one PCR and/or dedicated microarray) a limited number of gene targets involved in colorectal
      carcinogenesis is available. The investigators will collect stools, urine, and blood in a
      period of 15 to 2 days prior to colonoscopy. The colonoscopy is performed in 50-74 years old
      asymptomatic individuals who have presented with a positive FOBT test under mass screening
      organisation. A final point will be performed 5 years after entry in the trial for all 1000
      individuals in order to check occurrence (alternative absence) of any disease during this
      period and the type of the disease for those individuals who will be shown with normal
      colonoscopy and to verify evolution of those who will presented with a colon or rectal tumor.
      Likelihood value of marker in diseases occurring during the survey period will be calculated
      and prognostic values estimated in those with colon or rectal cancer.
    

Intervention name(s): COLOHYBRITEST OR VALIHYBRITEST
Intervention type(s): Device
Intervention description(s): Detection of human colon or rectal tumours by using a simplified molecular test based on either a combination of methylated DNA or protein marker(s) alone or considered together in biological fluids like blood, urine and stools
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        population of asymptomatic subjects selected by a positive faecal occult blood test (FOBT)
        to undergo colonoscopy
      
Biospecimen description: 
      Blood, Serum Urine, Stools Tissues