title: High cancer risk and increased mortality in patients with Peutz-Jeghers syndrome.
abstract: BACKGROUND
  Peutz-Jeghers syndrome (PJS) is associated with an increased cancer risk. As the determination of optimal surveillance strategies is hampered by wide ranges in cancer risk estimates and lack of data on cancer-related mortality, we assessed cancer risks and mortality in a large cohort of patients with PJS.
  
  
  METHODS
  Dutch PJS patients were included in this cohort study. Patients were followed prospectively between January 1995 and July 2009, and clinical data from the period before 1995 were collected retrospectively. Data were obtained by interview and chart review. Cumulative cancer risks were calculated by Kaplan-Meier analysis and relative cancer and mortality risks by Poisson regression analysis.
  
  
  RESULTS
  We included 133 PJS patients (48% males) from 54 families, contributing 5004 person-years of follow-up. 49 cancers were diagnosed in 42 patients (32%), including 25 gastrointestinal (GI) cancers. The median age at first cancer diagnosis was 45 years. The cumulative cancer risk was 20% at age 40 (GI cancer 12%), increasing to 76% at age 70 (GI cancer 51%). Cumulative cancer risks were higher for females than for males (p=0.005). The relative cancer risk was higher in PJS patients than in the general population (HR 8.96; 95% CI 6.46 to 12.42), and higher among female (HR 20.40; 95% CI 13.43 to 30.99) than among male patients (HR 4.76; 95% CI 2.82 to 8.04). 42 patients had died at a median age of 45 years, including 28 cancer-related deaths (67%). Mortality was increased in our cohort compared to the general population (HR 3.50; 95% CI 2.57 to 4.75).
  
  
  CONCLUSIONS
  PJS patients carry high cancer risks, leading to increased mortality. The malignancies occur particularly in the GI tract and develop at young age. These results justify surveillance in order to detect malignancies in an early phase to improve outcome.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Room Ba-393, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. m.g.f.vanlier@erasmusmc.nl
authors.forename: Margot G F
authors.initials: MG
authors.lastname: van Lier
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Westerman
authors.forename: Anja
authors.initials: A
authors.lastname: Wagner
authors.forename: Caspar W N
authors.initials: CW
authors.lastname: Looman
authors.forename: J H Paul
authors.initials: JH
authors.lastname: Wilson
authors.forename: Felix W M
authors.initials: FW
authors.lastname: de Rooij
authors.forename: Valery E P P
authors.initials: VE
authors.lastname: Lemmens
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Kuipers
authors.forename: Elisabeth M H
authors.initials: EM
authors.lastname: Mathus-Vliegen
authors.forename: Monique E
authors.initials: ME
authors.lastname: van Leerdam
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology; D004812:Epidemiologic Methods; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000453:epidemiology; D005833:Genital Neoplasms, Female / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009386:Neoplastic Syndromes, Hereditary / Q000175:diagnosis / Q000453:epidemiology; D009426:Netherlands / Q000453:epidemiology; D010580:Peutz-Jeghers Syndrome / Q000175:diagnosis / Q000453:epidemiology*