title: One to 2-year surveillance intervals reduce risk of colorectal cancer in families with Lynch syndrome.
abstract: OBJECTIVE
  Two percent to 4% of all cases of colorectal cancer (CRC) are associated with Lynch syndrome. Dominant clustering of CRC (non-Lynch syndrome) accounts for 1%-3% of the cases. Because carcinogenesis is accelerated in Lynch syndrome, an intensive colonoscopic surveillance program has been recommended since 1995. The aim of the study was to evaluate the effectiveness of this program.
  
  
  METHODS
  The study included 205 Lynch syndrome families with identified mutations in one of the mismatch repair genes (745 mutation carriers). We also analyzed data from non-Lynch syndrome families (46 families, 344 relatives). Patients were observed from January 1, 1995, until January 1, 2009. End points of the study were CRC or date of the last colonoscopy.
  
  
  RESULTS
  After a mean follow-up of 7.2 years, 33 patients developed CRC under surveillance. The cumulative risk of CRC was 6% after the 10-year follow-up period. The risk of CRC was higher in carriers older than 40 years and in carriers of MLH1 and MSH2 mutations. After a mean follow-up of 7.0 years, 6 cases of CRC were detected among non-Lynch syndrome families. The risk of CRC was significantly higher among families with Lynch syndrome, compared with those without.
  
  
  CONCLUSIONS
  With surveillance intervals of 1-2 years, members of families with Lynch syndrome have a lower risk of developing CRC than with surveillance intervals of 2-3 years. Because of the low risk of CRC in non-Lynch syndrome families, a less intensive surveillance protocol can be recommended.
authors.affiliation: The Netherlands Foundation for the Detection of Hereditary Tumours, Leiden, The Netherlands. hfavasen@stoet.nl
authors.forename: Hans F A
authors.initials: HF
authors.lastname: Vasen
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdirahman
authors.forename: Richard
authors.initials: R
authors.lastname: Brohet
authors.forename: Alexandra M J
authors.initials: AM
authors.lastname: Langers
authors.forename: Jan H
authors.initials: JH
authors.lastname: Kleibeuker
authors.forename: Mariette
authors.initials: M
authors.lastname: van Kouwen
authors.forename: Jan Jacob
authors.initials: JJ
authors.lastname: Koornstra
authors.forename: Henk
authors.initials: H
authors.lastname: Boot
authors.forename: Annemieke
authors.initials: A
authors.lastname: Cats
authors.forename: Evelien
authors.initials: E
authors.lastname: Dekker
authors.forename: Silvia
authors.initials: S
authors.lastname: Sanduleanu
authors.forename: Jan-Werner
authors.initials: JW
authors.lastname: Poley
authors.forename: James C H
authors.initials: JC
authors.lastname: Hardwick
authors.forename: Wouter H
authors.initials: WH
authors.lastname: de Vos Tot Nederveen Cappel
authors.forename: Andrea E
authors.initials: AE
authors.lastname: van der Meulen-de Jong
authors.forename: T Gie
authors.initials: TG
authors.lastname: Tan
authors.forename: Maarten A J M
authors.initials: MA
authors.lastname: Jacobs
authors.forename: Faig Lall A
authors.initials: FL
authors.lastname: Mohamed
authors.forename: Sijbrand Y
authors.initials: SY
authors.lastname: de Boer
authors.forename: Paul C
authors.initials: PC
authors.lastname: van de Meeberg
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Verhulst
authors.forename: Jan M
authors.initials: JM
authors.lastname: Salemans
authors.forename: Nico
authors.initials: N
authors.lastname: van Bentem
authors.forename: B Dik
authors.initials: BD
authors.lastname: Westerveld
authors.forename: Juda
authors.initials: J
authors.lastname: Vecht
authors.forename: Fokko M
authors.initials: FM
authors.lastname: Nagengast
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D012306:Risk; D013997:Time Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein