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Region Hovedstaden - en del af Københavns Universitetshospital
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Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Pål Møller
  • Toni Seppälä
  • Inge Bernstein
  • Elke Holinski-Feder
  • Paola Sala
  • D Gareth Evans
  • Annika Lindblom
  • Finlay Macrae
  • Ignacio Blanco
  • Rolf Sijmons
  • Jacqueline Jeffries
  • Hans Vasen
  • John Burn
  • Sigve Nakken
  • Eivind Hovig
  • Einar Andreas Rødland
  • Kukatharmini Tharmaratnam
  • Wouter H de Vos Tot Nederveen Cappel
  • James Hill
  • Juul Wijnen
  • Kate Green
  • Fiona Lalloo
  • Lone Sunde
  • Miriam Mints
  • Lucio Bertario
  • Marta Pineda
  • Matilde Navarro
  • Monika Morak
  • Laura Renkonen-Sinisalo
  • Ian M Frayling
  • John-Paul Plazzer
  • Kirsi Pylvanainen
  • Julian R Sampson
  • Gabriel Capella
  • Jukka-Pekka Mecklin
  • Gabriela Möslein
  • Mallorca Group (http://mallorca-group.eu)
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OBJECTIVE: Estimates of cancer risk and the effects of surveillance in Lynch syndrome have been subject to bias, partly through reliance on retrospective studies. We sought to establish more robust estimates in patients undergoing prospective cancer surveillance.

DESIGN: We undertook a multicentre study of patients carrying Lynch syndrome-associated mutations affecting MLH1, MSH2, MSH6 or PMS2. Standardised information on surveillance, cancers and outcomes were collated in an Oracle relational database and analysed by age, sex and mutated gene.

RESULTS: 1942 mutation carriers without previous cancer had follow-up including colonoscopic surveillance for 13 782 observation years. 314 patients developed cancer, mostly colorectal (n=151), endometrial (n=72) and ovarian (n=19). Cancers were detected from 25 years onwards in MLH1 and MSH2 mutation carriers, and from about 40 years in MSH6 and PMS2 carriers. Among first cancer detected in each patient the colorectal cancer cumulative incidences at 70 years by gene were 46%, 35%, 20% and 10% for MLH1, MSH2, MSH6 and PMS2 mutation carriers, respectively. The equivalent cumulative incidences for endometrial cancer were 34%, 51%, 49% and 24%; and for ovarian cancer 11%, 15%, 0% and 0%. Ten-year crude survival was 87% after any cancer, 91% if the first cancer was colorectal, 98% if endometrial and 89% if ovarian.

CONCLUSIONS: The four Lynch syndrome-associated genes had different penetrance and expression. Colorectal cancer occurred frequently despite colonoscopic surveillance but resulted in few deaths. Using our data, a website has been established at http://LScarisk.org enabling calculation of cumulative cancer risks as an aid to genetic counselling in Lynch syndrome.

OriginalsprogEngelsk
TidsskriftGut
Vol/bind66
Udgave nummer3
Sider (fra-til)464-472
ISSN0017-5749
DOI
StatusUdgivet - mar. 2017

ID: 45902204