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Genetic and clinical characterisation of familial adenomatous polyposis: a population based study
  1. A-L Moisio1,
  2. H Järvinen2,
  3. P Peltomäki3
  1. 1Department of Medical Genetics, Biomedicum Helsinki, PO Box 63, FIN-00014 University of Helsinki, Finland
  2. 2Second Department of Surgery, PO Box 260, FIN-00029 Helsinki University Central Hospital, Finland
  3. 3Division of Human Cancer Genetics, Ohio State University, 420 West 12th Avenue, Columbus, Ohio 43210, USA and Department of Medical Genetics, Biomedicum Helsinki, PO Box 63, FIN-00014 University of Helsinki, Finland
  1. Corresponding author:
    Dr A-L Moisio, Department of Medical Genetics, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FIN-00014 University of Helsinki, Finland;


Background: Familial adenomatous polyposis (FAP) is a rare autosomal dominantly inherited disease predisposing to colon cancer and caused by germline mutations in the APC (adenomatous polyposis coli) gene.

Aims: We conducted a population based study to evaluate the prevalence and clinical implications of APC mutations among Finnish FAP kindreds. A possible founder effect in parallel with previous observations in hereditary non-polyposis colon cancer (HNPCC) was addressed.

Patients: Affected individuals from 65 kindreds were included.

Methods: The APC gene was screened for mutations using the protein truncation test and heteroduplex analysis. Haplotype analysis was performed with four flanking microsatellite markers. Families that failed to show any mutations were scrutinised with Southern blot hybridisation and allelic expression analysis.

Results: Thirty eight different germline mutations in APC were identified in 47 kindreds (72%). The majority of these mutations were novel and unique to each family. Although sharing the classical polyposis phenotype, families without detectable APC mutations differed from mutation positive families in the following respects: firstly, mean age at polyposis diagnosis was higher (38.6 years (48 individuals) v 30.0 years (140 individuals); p=0.001); and secondly, the proportion of kindreds lacking extracolonic disease was higher (6/18 v 5/47; p=0.04).

Conclusions: Our results may pave the way for predictive testing in mutation positive families and should stimulate further molecular studies in mutation negative families. No founder effect was observed, which is in contrast with HNPCC in the same population.

  • adenomatous polyposis coli
  • familial adenomatous polyposis
  • founder effect
  • mutation analysis
  • AAPC, attenuated adenomatous polyposis coli
  • APC gene, adenomatous polyposis coli gene
  • FAP, familial adenomatous polyposis
  • HNPCC, hereditary non-polyposis colorectal cancer
  • PAGE, polyacrylamide gel electrophoresis
  • PCR, polymerase chain reaction
  • PTT, protein truncation test
  • RT, reverse transcription
  • Wnt/wg, mammalian homologue (Wnt) for Drosophila wingless (Wg)

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