A Multicenter Clinical Trial of Stool-based DNA Testing for Early Detection of Colon Cancer in China
Condition: Colorectal Cancer; Advanced Adenocarcinoma; Hyperplastic Polyp; Colorectal Neoplasms; Digestive System Neoplasm; Neoplasms
MeSH terms: Neoplasms; Colorectal Neoplasms; Digestive System Neoplasms; Gastrointestinal Neoplasms
Study type: Observational [Patient Registry]

Summary: 
      According to data from Global Cancer Statistics 2018, colorectal cancer (CRC) ranks second in
      incidence and fifth in mortality among all cancers in China. The underlying neoplastic
      progression from adenoma to CRC endures up to 10 years, providing an extended window for CRC
      detection and screening. Currently, fecal occult blood test (FOBT) and colonoscopy are the
      main diagnostic and screening methods for CRC in Chinese clinical practice. However, due to
      low patients' compliance with colonoscopy and poor sensitivity of FOBT, a large proportion of
      CRC could not be effectively diagnosed and treated at early stage. Therefore, noninvasive
      fecal DNA detection approach with enhanced performance is urgently needed in clinic.

      The aim of this trial is to evaluate effectiveness of the Human Multigene Methylation
      Detection Kit (Fluorescent PCR) for auxiliary diagnosis of colorectal cancer. By assessing
      the level of DNA methylation of certain genes in human stool, the test can indicate whether
      cancerous and precancerous lesions exist in the areas of colon and rectum.
    

Detailed description: 
      The multicenter clinical trial will be conducted using a single-blind method. Stool samples
      provided by participants will be evaluated by Human Multigene Methylation Detection Kit
      (Fluorescent PCR). The kit will be used to qualitatively detect methylation levels of
      multiple genes in human stool samples in vitro by using Quantitative Methylation Specific PCR
      (qMSP). The principle of the method is as follows. First, the target DNA in human stool is
      extracted by magnetic bead-capture technology and then treated with sodium bisulfite. The
      sequence of unmethylated DNA will be changed while that of the methylated DNA remains the
      same after sodium bisulfite treatment. Subsequently, qMSP is employed to detect methylation
      levels of target genes in addition to ACTB gene (a reference gene). Controls of ACTB gene
      with and without methylation are tested simultaneously. Result of qMSP is dichotomized as
      positive and negative based on Ct value obtained. The test result is then verified by Sanger
      sequencing and compared with that from colonoscopy examination and pathology report. The main
      evaluation indexes for test performance are sensitivity, specificity, consistency rate, kappa
      coefficient.
    

Intervention name(s): Multigene Methylation Detection Kit
Intervention type(s): Diagnostic Test
Intervention description(s): Eligible participants are required to take stool samples for multigene methylation detection and gene sequencing, undergo colonoscopy examination, and have a biopsy when necessary (gold standard).
Other intervention name(s): Colosafe 2.0
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Participants aged 40-79 years old, regardless of gender or region, and those who meet the
        inclusion criteria for this clinical trial, are eligible to enroll at the designated
        clinical sites. Up to 1113 participants will be enrolled.
      
Biospecimen description: 
      Isolated human DNA from stool samples
    
Keywords: Colorectal Cancer; Colon Cancer; Stool DNA test; fecal DNA test; Methylation Biomarkers; Colonoscopy; Cancer Screening