title: Stool Investigations for Colorectal Cancer Screening: From Occult Blood Test to DNA Analysis.
abstract: OBJECTIVE
  We report an update of current methods for colorectal cancer (CRC) screening based on fecal sample analysis.
  
  
  METHODS
  A systematic review of the literature was performed in MEDLINE, EMBASE, and Science Direct electronic databases.
  
  
  RESULTS
  Blood in the stools is the first and most used strategy. Fecal occult blood test (FOBT) and fecal immunochemical test (FIT) are the main methods. Both are economic, easy to perform with high specificity, and low sensitivity. Based on CRC multi-step process with genetic and epigenetic alterations in large bowel cell DNA, single mutations or panels of alterations have been detected. These tests have the advantage of a marked improvement of the sensitivity when compared to fecal blood. However, high costs, poor availability, and correct choice of marker panel represent the major limits. A specific sDNA panel including aberrantly methylated BMP3 and NDRG4 promoter regions, mutant k-ras and β-actin (a reference gene for human DNA quantity), and an immunochemical assay for human hemoglobin has been recently approved by Food and Drug Administration. Novel promising biomarkers for CRC screening are represented by microRNAs (miRNAs), a group of 18-25 nucleotide non-coding RNA molecules that regulate gene expression. Reports on these fecal biomarkers are case-control studies, and each of them evaluates single miRNAs or multi-target panels. On the other hand, some fecal proteins have been studied as possible CRC screening markers, even though they demonstrated poor results. Finally, alterations of estrogen receptor-beta (i.e., dramatic reduction in the early stage of CRC) have been demonstrated in tissue samples.
  
  
  CONCLUSIONS
  Specific investigations are warranted in order to add further noninvasive markers to the panel of CRC screening tools.
authors.affiliation: Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Iannone
authors.affiliation: Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Losurdo
authors.affiliation: Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Pricci
authors.affiliation: Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Bruna
authors.initials: B
authors.lastname: Girardi
authors.affiliation: Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Massaro
authors.affiliation: Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Mariabeatrice
authors.initials: M
authors.lastname: Principi
authors.affiliation: Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Barone
authors.affiliation: Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Ierardi
authors.affiliation: Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy. a.dileo@gastro.uniba.it.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Di Leo
mesh_terms: D015179:Colorectal Neoplasms / Q000175:diagnosis*; D004247:DNA / Q000032:analysis*; D055088:Early Detection of Cancer / Q000379:methods*; D005243:Feces / Q000166:cytology*; D006801:Humans; D008403:Mass Screening / Q000379:methods*; D009780:Occult Blood
chemical_list: D004247:DNA
keywords: Adenoma; Colorectal cancer; Fecal DNA; Fecal immunochemical test; Fecal occult blood test; Screening