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The Capital Region of Denmark - a part of Copenhagen University Hospital

An alternative approach to establishing unbiased colorectal cancer risk estimation in Lynch syndrome

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Use of primary health care and participation in colorectal cancer screening - a Danish national register-based study

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  2. Benefit from extended surveillance interval on colorectal cancer risk in Lynch syndrome

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  3. Broadening risk profile in familial colorectal cancer type X; increased risk for five cancer types in the national Danish cohort

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  4. Characterization of burning mouth syndrome profiles based on response to a local anaesthetic lozenge

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Manon Suerink
  • Mar Rodríguez-Girondo
  • Heleen M van der Klift
  • Chrystelle Colas
  • Laurence Brugieres
  • Noémie Lavoine
  • Marjolijn Jongmans
  • Gabriel Capellá Munar
  • D Gareth Evans
  • Michael P Farrell
  • Maurizio Genuardi
  • Yael Goldberg
  • Encarna Gomez-Garcia
  • Karl Heinimann
  • Jessica I Hoell
  • Stefan Aretz
  • Kory W Jasperson
  • Inbal Kedar
  • Mitul B Modi
  • Sergey Nikolaev
  • Theo A M van Os
  • Tim Ripperger
  • Daniel Rueda
  • Leigha Senter
  • Wenche Sjursen
  • Lone Sunde
  • Christina Therkildsen
  • Maria G Tibiletti
  • Alison H Trainer
  • Yvonne J Vos
  • Anja Wagner
  • Ingrid Winship
  • Katharina Wimmer
  • Stefanie Y Zimmermann
  • Hans F Vasen
  • Christi J van Asperen
  • Jeanine J Houwing-Duistermaat
  • Sanne W Ten Broeke
  • Maartje Nielsen
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PURPOSE: Biallelic pathogenic variants in the mismatch repair (MMR) genes cause a recessive childhood cancer predisposition syndrome known as constitutional mismatch repair deficiency (CMMRD). Family members with a heterozygous MMR variant have Lynch syndrome. We aimed at estimating cancer risk in these heterozygous carriers as a novel approach to avoid complicated statistical methods to correct for ascertainment bias.

METHODS: Cumulative colorectal cancer incidence was estimated in a cohort of PMS2- and MSH6-associated families, ascertained by the CMMRD phenotype of the index, by using mutation probabilities based on kinship coefficients as analytical weights in a proportional hazard regression on the cause-specific hazards. Confidence intervals (CIs) were obtained by bootstrapping at the family level.

RESULTS: The estimated cumulative colorectal cancer risk at age 70 years for heterozygous PMS2 variant carriers was 8.7% (95% CI 4.3-12.7%) for both sexes combined, and 9.9% (95% CI 4.9-15.3%) for men and 5.9% (95% CI 1.6-11.1%) for women separately. For heterozygous MSH6 variant carriers these estimates are 11.8% (95% CI 4.5-22.7%) for both sexes combined, 10.0% (95% CI 1.83-24.5%) for men and 11.7% (95% CI 2.10-26.5%) for women.

CONCLUSION: Our findings are consistent with previous reports that used more complex statistical methods to correct for ascertainment bias. These results underline the need for MMR gene-specific surveillance protocols for Lynch syndrome.

Original languageEnglish
JournalGenetics in medicine : official journal of the American College of Medical Genetics
Issue number12
Pages (from-to)2706-2712
Number of pages7
Publication statusPublished - Dec 2019

    Research areas

  • bMMRD, colon cancer risk, HNPCC, MSH6, PMS2

ID: 57376725