title: Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer.
abstract: BACKGROUND
  As screening methods for colorectal cancer (CRC) are limited by uptake and adherence, further options are sought. A blood test might increase both, but none has yet been tested in a screening setting.
  
  
  OBJECTIVE
  We prospectively assessed the accuracy of circulating methylated SEPT9 DNA (mSEPT9) for detecting CRC in a screening population.
  
  
  METHODS
  Asymptomatic individuals ≥50 years old scheduled for screening colonoscopy at 32 US and German clinics voluntarily gave blood plasma samples before colon preparation. Using a commercially available assay, three independent blinded laboratories assayed plasma DNA of all CRC cases and a stratified random sample of other subjects in duplicate real time PCRs. The primary outcomes measures were standardised for overall sensitivity and specificity estimates.
  
  
  RESULTS
  7941 men (45%) and women (55%), mean age 60 years, enrolled. Results from 53 CRC cases and from 1457 subjects without CRC yielded a standardised sensitivity of 48.2% (95% CI 32.4% to 63.6%; crude rate 50.9%); for CRC stages I-IV, values were 35.0%, 63.0%, 46.0% and 77.4%, respectively. Specificity was 91.5% (95% CI 89.7% to 93.1%; crude rate 91.4%). Sensitivity for advanced adenomas was low (11.2%).
  
  
  CONCLUSIONS
  Our study using the blood based mSEPT9 test showed that CRC signal in blood can be detected in asymptomatic average risk individuals undergoing screening. However, the utility of the test for population screening for CRC will require improved sensitivity for detection of early cancers and advanced adenomas.
  
  
  BACKGROUND
  NCT00855348.
authors: Department of Environmental Health Sciences, University of Minnesota School of Public Health, , Minneapolis, Minnesota, USA.
authors: Timothy Robert
authors: TR
authors: Church
authors: Michael
authors: M
authors: Wandell
authors: Catherine
authors: C
authors: Lofton-Day
authors: Steven J
authors: SJ
authors: Mongin
authors: Matthias
authors: M
authors: Burger
authors: Shannon R
authors: SR
authors: Payne
authors: Esmeralda
authors: E
authors: Castaños-Vélez
authors: Brent A
authors: BA
authors: Blumenstein
authors: Thomas
authors: T
authors: Rösch
authors: Neal
authors: N
authors: Osborn
authors: Dale
authors: D
authors: Snover
authors: Robert W
authors: RW
authors: Day
authors: David F
authors: DF
authors: Ransohoff
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics; D019175:DNA Methylation; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D058112:Septins / Q000097:blood*; D014481:United States
chemical_list: D014408:Biomarkers, Tumor; C474315:SEPTIN9 protein, human; D058112:Septins
keywords: Colonoscopy; Colorectal Adenomas; Colorectal Cancer Screening; Colorectal Neoplasm; Methylation