title: An effect from anticipation also in hereditary nonpolyposis colorectal cancer families without identified mutations.
abstract: Optimal prevention of hereditary cancer is central and requires initiation of surveillance programmes and/or prophylactic measures at a safe age. Anticipation, expressed as an earlier age at onset in successive generations, has been demonstrated in hereditary nonpolyposis colorectal cancer (HNPCC). We specifically addressed anticipation in phenotypic HNPCC families without disease-predisposing mismatch repair (MMR) defects since risk estimates and age at onset are particularly difficult to determine in this cohort. The national Danish HNPCC register was used to identify families who fulfilled the Amsterdam criteria for HNPCC and showed normal MMR function and/or lack of disease-predisposing MMR gene mutation. In total, 319 cancers from 212 parent-child pairs in 99 families were identified. A paired t-test and a bivariate statistical model were used to assess anticipation. Both methods demonstrated an effect from anticipation with cancer diagnosed mean 11.4 years (t-test, p<0.0001) and mean 5.9 (bivariate model, p=0.02) years earlier in children than in parents. This observation suggests that anticipation may apply also to families without identified mutations and serves as a reminder to initiate surveillance programmes at young age also in HNPCC families with undefined genetic causes.
authors.affiliation: HNPCC-Register, Department of Gastroenterology, Hvidovre University Hospital, Copenhagen University, Denmark.
authors.forename: Susanne
authors.initials: S
authors.lastname: Timshel
authors.forename: Christina
authors.initials: C
authors.lastname: Therkildsen
authors.forename: Pär-Ola
authors.initials: PO
authors.lastname: Bendahl
authors.forename: Inge
authors.initials: I
authors.lastname: Bernstein
authors.forename: Mef
authors.initials: M
authors.lastname: Nilbert
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D020132:Anticipation, Genetic; D002648:Child; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D053843:DNA Mismatch Repair; D003718:Denmark; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009154:Mutation; D010290:Parents; D010641:Phenotype; D012042:Registries; D055815:Young Adult