Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
E-pub ahead of print

Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database

Research output: Contribution to journalJournal articleResearchpeer-review

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

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Correction: The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin-Siris syndrome

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin-Siris syndrome

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Noncardiac genetic predisposition in sudden infant death syndrome

    Research output: Contribution to journalJournal articleResearchpeer-review

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

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Global microRNA profiling of metastatic conjunctival melanoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Gentagne diploid biparental molae

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. The genetic evolution of metastatic uveal melanoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Mev Dominguez-Valentin
  • Julian R Sampson
  • Toni T Seppälä
  • Sanne W Ten Broeke
  • John-Paul Plazzer
  • Sigve Nakken
  • Christoph Engel
  • Stefan Aretz
  • Mark A Jenkins
  • Lone Sunde
  • Inge Bernstein
  • Gabriel Capella
  • Francesc Balaguer
  • Huw Thomas
  • D Gareth Evans
  • John Burn
  • Marc Greenblatt
  • Eivind Hovig
  • Wouter H de Vos Tot Nederveen Cappel
  • Rolf H Sijmons
  • Lucio Bertario
  • Maria Grazia Tibiletti
  • Giulia Martina Cavestro
  • Annika Lindblom
  • Adriana Della Valle
  • Francisco Lopez-Köstner
  • Nathan Gluck
  • Lior H Katz
  • Karl Heinimann
  • Carlos A Vaccaro
  • Reinhard Büttner
  • Heike Görgens
  • Elke Holinski-Feder
  • Monika Morak
  • Stefanie Holzapfel
  • Robert Hüneburg
  • Magnus von Knebel Doeberitz
  • Markus Loeffler
  • Nils Rahner
  • Hans K Schackert
  • Verena Steinke-Lange
  • Wolff Schmiegel
  • Deepak Vangala
  • Kirsi Pylvänäinen
  • Laura Renkonen-Sinisalo
  • John L Hopper
  • Aung Ko Win
  • Robert W Haile
  • Noralane M Lindor
  • Steven Gallinger
  • Loïc Le Marchand
  • Polly A Newcomb
  • Jane C Figueiredo
  • Stephen N Thibodeau
  • Karin Wadt
  • Christina Therkildsen
  • Henrik Okkels
  • Zohreh Ketabi
  • Leticia Moreira
  • Ariadna Sánchez
  • Miquel Serra-Burriel
  • Marta Pineda
  • Matilde Navarro
  • Ignacio Blanco
  • Kate Green
  • Fiona Lalloo
  • Emma J Crosbie
  • James Hill
  • Oliver G Denton
  • Ian M Frayling
  • Einar Andreas Rødland
  • Hans Vasen
  • Miriam Mints
  • Florencia Neffa
  • Patricia Esperon
  • Karin Alvarez
  • Revital Kariv
  • Guy Rosner
  • Tamara Alejandra Pinero
  • María Laura Gonzalez
  • Pablo Kalfayan
  • Douglas Tjandra
  • Ingrid M Winship
  • Finlay Macrae
  • Gabriela Möslein
  • Jukka-Pekka Mecklin
  • Maartje Nielsen
  • Pål Møller
View graph of relations

PURPOSE: Pathogenic variants affecting MLH1, MSH2, MSH6, and PMS2 cause Lynch syndrome and result in different but imprecisely known cancer risks. This study aimed to provide age and organ-specific cancer risks according to gene and gender and to determine survival after cancer.

METHODS: We conducted an international, multicenter prospective observational study using independent test and validation cohorts of carriers of class 4 or class 5 variants. After validation the cohorts were merged providing 6350 participants and 51,646 follow-up years.

RESULTS: There were 1808 prospectively observed cancers. Pathogenic MLH1 and MSH2 variants caused high penetrance dominant cancer syndromes sharing similar colorectal, endometrial, and ovarian cancer risks, but older MSH2 carriers had higher risk of cancers of the upper urinary tract, upper gastrointestinal tract, brain, and particularly prostate. Pathogenic MSH6 variants caused a sex-limited trait with high endometrial cancer risk but only modestly increased colorectal cancer risk in both genders. We did not demonstrate a significantly increased cancer risk in carriers of pathogenic PMS2 variants. Ten-year crude survival was over 80% following colon, endometrial, or ovarian cancer.

CONCLUSION: Management guidelines for Lynch syndrome may require revision in light of these different gene and gender-specific risks and the good prognosis for the most commonly associated cancers.

Original languageEnglish
JournalGenetics in medicine : official journal of the American College of Medical Genetics
ISSN1098-3600
DOIs
Publication statusE-pub ahead of print - 24 Jul 2019

    Research areas

  • Lynch syndrome, MLH1, MSH2, MSH6, PMS2

ID: 57712602