title: Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer.
abstract: OBJECTIVE
  Identification of the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome enables prevention of colorectal cancer (CRC) by means of colonoscopy and polypectomies. We evaluated the efficacy of screening in a controlled trial over 15 years.
  
  
  METHODS
  Incidence of CRC and survival were compared in 2 cohorts of at-risk members of 22 families with HNPCC. Colonic screening at 3-year intervals was arranged for 133 subjects; 119 control subjects had no screening. Genetic testing was offered to subjects in whose families the causative mutation was known.
  
  
  RESULTS
  CRC developed in 8 screened subjects (6%) compared with 19 control subjects (16 %; P = 0.014). The CRC rate was reduced by 62%. In mutation-positive subjects alone, the CRC rates were 18% in screened subjects and 41% in controls (P = 0.02). The decrease resulted from the removal of adenomas in 13 mutation-positive individuals (30%) and in 6 subjects with unknown mutation status (40%). All CRCs in the study group were local, causing no deaths, compared with 9 deaths caused by CRC in the controls. The overall death rates were 10 vs. 26 subjects in the study and control groups (P = 0.003), 4 vs. 12 in mutation-positive subjects (P = 0.05).
  
  
  CONCLUSIONS
  Colonoscopic screening at 3-year intervals more than halves the risk of CRC, prevents CRC deaths, and decreases overall mortality by about 65% in HNPCC families.
authors.affiliation: Second Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: H J
authors.initials: HJ
authors.lastname: Järvinen
authors.forename: M
authors.initials: M
authors.lastname: Aarnio
authors.forename: H
authors.initials: H
authors.lastname: Mustonen
authors.forename: K
authors.initials: K
authors.lastname: Aktan-Collan
authors.forename: L A
authors.initials: LA
authors.lastname: Aaltonen
authors.forename: P
authors.initials: P
authors.lastname: Peltomäki
authors.forename: A
authors.initials: A
authors.lastname: De La Chapelle
authors.forename: J P
authors.initials: JP
authors.lastname: Mecklin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D002352:Carrier Proteins; D003113:Colonoscopy; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology* / Q000235:genetics / Q000401:mortality / Q000517:prevention & control; D005260:Female; D006801:Humans; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D011446:Prospective Studies; D012306:Risk; D012812:Sigmoidoscopy
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1