title: Prospective results of surveillance colonoscopy in dominant familial colorectal cancer with and without Lynch syndrome.
abstract: OBJECTIVE
  Lynch syndrome is an autosomal dominant predisposition to colorectal cancer caused by mutations in DNA mismatch repair genes; colorectal cancer risk is high. Few studies have addressed colorectal cancer risk in individuals from dominant families without mismatch repair deficiency. We sought to establish whether these individuals are also at increased risk by examining the incidence of advanced neoplasia during surveillance.
  
  
  METHODS
  In this prospective cohort study, BAT26 testing of tumors was carried out at 2 tertiary centers on 125 individuals from 97 families (with a dominant colorectal cancer history) to classify families as Lynch syndrome (microsatellite unstable) or non-Lynch syndrome (microsatellite stable). Colonoscopy results in 288 at-risk family members were compared.
  
  
  RESULTS
  Twenty-nine families were classified as Lynch syndrome and 68 as non-Lynch syndrome. Seven hundred seventy-six colonoscopies were undertaken. High-risk adenomas occurred in 7 of 91 (7.7%) Lynch syndrome individuals and 15 of 197 (7.6%) non-Lynch syndrome individuals, adjusted relative risk 1.15 (95% CI: 0.6-2.3). Cancer was observed only in Lynch syndrome individuals (4/91; 4.4%), Fisher exact test, P = .010. Multiple adenomas were only seen in non-Lynch syndrome individuals (13/197; 6.6%), Fisher exact text, P = .06.
  
  
  CONCLUSIONS
  Individuals with an autosomal dominant family history of colorectal cancer with and without evidence of Lynch syndrome are at equal risk of high-risk adenomas during surveillance, but colorectal cancer was only seen in Lynch syndrome. Therefore non-Lynch syndrome individuals do require colonoscopic surveillance, but the interval could be lengthened because risk of (interval) cancer is low. Lynch syndrome individuals require short surveillance intervals as is the recommended practice.
authors.affiliation: Family Cancer Group, Cancer Research, UK Colorectal Cancer Unit, St. Mark's Hospital, Watford Road, Harrow, Middlesex, United Kingdom.
authors.forename: Isis
authors.initials: I
authors.lastname: Dove-Edwin
authors.forename: Andrea E
authors.initials: AE
authors.lastname: de Jong
authors.forename: Joanna
authors.initials: J
authors.lastname: Adams
authors.forename: David
authors.initials: D
authors.lastname: Mesher
authors.forename: Lara
authors.initials: L
authors.lastname: Lipton
authors.forename: Peter
authors.initials: P
authors.lastname: Sasieni
authors.forename: Hans F A
authors.initials: HF
authors.lastname: Vasen
authors.forename: Huw J W
authors.initials: HJ
authors.lastname: Thomas
mesh_terms: D017677:Age Distribution; D020137:Base Pair Mismatch; D015331:Cohort Studies; D003113:Colonoscopy / Q000379:methods; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005820:Genetic Testing; D006801:Humans; D015994:Incidence; D008297:Male; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D010375:Pedigree; D011379:Prognosis; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D017678:Sex Distribution
chemical_list: D051718:MutS Homolog 2 Protein