title: Markers of the APC/β-catenin signaling pathway as potential treatable, preneoplastic biomarkers of risk for colorectal neoplasms.
abstract: BACKGROUND
  Malfunctioning of the adenomatous polyposis coli (APC)/β-catenin signaling pathway is both an early and common event in sporadic colorectal cancer. To assess the potential of APC/β-catenin signaling pathway markers as treatable, preneoplastic biomarkers of risk for colorectal neoplasms, we conducted a pilot colonoscopy-based case-control study (51 cases and 154 controls) of incident, sporadic colorectal adenoma.
  
  
  METHODS
  We evaluated APC, β-catenin, and E-cadherin expression in normal mucosa from the rectum and ascending and sigmoid colon using automated immunohistochemical and quantitative image analysis. Diet, lifestyle, and medical history were assessed with validated questionnaires.
  
  
  RESULTS
  In the normal rectal mucosa, the ratio of the proportion of APC expression in the upper 40% of crypts with total β-catenin expression (APC/β-catenin score) was 14.3% greater in controls than in cases [P = 0.02; OR, 0.40; 95% confidence interval (CI), 0.14-1.14]. Compared with controls, in cases, APC expression was 3.2% lower, β-catenin expression was 3.0% higher, and E-cadherin expression was 0.7% lower; however, none of these differences were statistically significant. The APC/β-catenin score statistically significantly differed according to categories of plausible risk factors for colorectal cancer [e.g., it was 17.7% higher among those with 25(OH) vitamin D(3) concentrations ≥ 27 ng/mL].
  
  
  CONCLUSIONS
  These preliminary data suggest that the combined expression of APC and β-catenin in the normal rectal mucosa may be associated with risk for incident, sporadic colorectal neoplasms, as well as with modifiable risk factors for colorectal neoplasms.
  
  
  CONCLUSIONS
  Our results may help advance the development of treatable, preneoplastic biomarkers of risk for colorectal neoplasms.
authors.affiliation: Rollins School of Public Health, Emory University, Atlanta, GA, USA.
authors.forename: Thomas U
authors.initials: TU
authors.lastname: Ahearn
authors.forename: Aasma
authors.initials: A
authors.lastname: Shaukat
authors.forename: W Dana
authors.initials: WD
authors.lastname: Flanders
authors.forename: March E
authors.initials: ME
authors.lastname: Seabrook
authors.forename: Roberd M
authors.initials: RM
authors.lastname: Bostick
mesh_terms: D015650:24,25-Dihydroxyvitamin D 3 / Q000097:blood; D011125:Adenomatous Polyposis Coli / Q000097:blood / Q000378:metabolism; D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D016022:Case-Control Studies; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012307:Risk Factors; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D014408:Biomarkers, Tumor; D015820:Cadherins; D051176:beta Catenin; D015650:24,25-Dihydroxyvitamin D 3