title: Truncating mutations in Peutz-Jeghers syndrome are associated with more polyps, surgical interventions and cancers.
abstract: OBJECTIVE
  Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant polyposis syndrome caused by STK11 germline mutations. PJS is associated with an increased risk of cancer. In our cohort, clinical and phenotypic parameters were correlated with genotypic findings and patients were prospectively followed by surveillance.
  
  
  METHODS
  Thirty-one patients treated between 2000 and 2006, were evaluated. STK11 genotyping was performed and phenotypes of patients with truncating (TM) and nontruncating mutations (NTM) were compared.
  
  
  RESULTS
  Median age at first symptoms was 11 years and complications occurred before the age of ten in 42% of patients. STK11 mutations were detected in 16 of 22 families (12 TM; four NTM). Patients with TM had more surgical gastrointestinal (GI) interventions (p = 0.021), and female patients in the TM group had an increased risk of undergoing gynecological surgery (p = 0.016). Also, there was a trend towards a higher polyp count (p = 0.11) and earlier age at first polypectomy (p = 0.13) in the TM group. Ten carcinomas were detected in six patients resulting in a cancer risk of 65% up to the age of 65 years. Patients with TM tended to develop more cancers (p = 0.10). Importantly, our surveillance strategy used detected 50% of cancers (n = 5) at an early potentially curable stage.
  
  
  CONCLUSIONS
  Our study shows that almost half of PJ patients have complications early in life independent of mutational status. Patients with TM require more surgical GI interventions and tend to develop more polyps and cancers. Furthermore, close surveillance detects early stage cancers in patients. We propose that surveillance should be started as early as 8 years in all patients to avoid complications. Moreover, patients with TM may benefit from surveillance at shorter intervals.
authors.affiliation: Medical Department, Knappschaftskrankenhaus, Ruhr-University Bochum, Germany.
authors.forename: Heidi
authors.initials: H
authors.lastname: Salloch
authors.forename: Anke
authors.initials: A
authors.lastname: Reinacher-Schick
authors.forename: Karsten
authors.initials: K
authors.lastname: Schulmann
authors.forename: Christian
authors.initials: C
authors.lastname: Pox
authors.forename: Jörg
authors.initials: J
authors.lastname: Willert
authors.forename: Andrea
authors.initials: A
authors.lastname: Tannapfel
authors.forename: Stefan
authors.initials: S
authors.lastname: Heringlake
authors.forename: Timm O
authors.initials: TO
authors.lastname: Goecke
authors.forename: Stefan
authors.initials: S
authors.lastname: Aretz
authors.forename: Susanne
authors.initials: S
authors.lastname: Stemmler
authors.forename: Wolff
authors.initials: W
authors.lastname: Schmiegel
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D002648:Child; D002675:Child, Preschool; D003110:Colonic Neoplasms / Q000150:complications* / Q000453:epidemiology / Q000601:surgery*; D003111:Colonic Polyps / Q000150:complications* / Q000453:epidemiology / Q000601:surgery*; D005260:Female; D056726:Genetic Association Studies; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010580:Peutz-Jeghers Syndrome / Q000150:complications* / Q000453:epidemiology / Q000235:genetics* / Q000601:surgery; D055815:Young Adult