Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer

Gastroenterology. 2000 May;118(5):829-34. doi: 10.1016/s0016-5085(00)70168-5.

Abstract

Background & aims: 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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Carrier Proteins
  • Colonoscopy
  • Colorectal Neoplasms, Hereditary Nonpolyposis / epidemiology*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / mortality
  • Colorectal Neoplasms, Hereditary Nonpolyposis / prevention & control
  • Female
  • Humans
  • Male
  • Mass Screening
  • Middle Aged
  • MutL Protein Homolog 1
  • Mutation
  • Neoplasm Proteins / genetics
  • Nuclear Proteins
  • Prospective Studies
  • Risk
  • Sigmoidoscopy

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • MLH1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • MutL Protein Homolog 1