The effect of genotypes and parent of origin on cancer risk and age of cancer development in PMS2 mutation carriers

Manon Suerink, Heleen M van der Klift, Sanne W Ten Broeke, Olaf M Dekkers, Inge Bernstein, Gabriel Capellá Munar, Encarna Gomez Garcia, Nicoline Hoogerbrugge, Tom G W Letteboer, Fred H Menko, Annika Lindblom, Arjen Mensenkamp, Pal Moller, Theo A van Os, Nils Rahner, Bert J W Redeker, Maran Olderode, Liesbeth Spruijt, Yvonne J Vos, Anja WagnerHans Morreau, Frederik J Hes, Hans F A Vasen, Carli M Tops, Juul T Wijnen, Maartje Nielsen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

15 Citationer (Scopus)

Abstract

PURPOSE: Lynch syndrome (LS), a heritable disorder with an increased risk of primarily colorectal cancer (CRC) and endometrial cancer (EC), can be caused by mutations in the PMS2 gene. We wished to establish whether genotype and/or parent-of-origin effects (POE) explain (part of) the reported variability in severity of the phenotype.

METHODS: European PMS2 mutation carriers (n = 381) were grouped and compared based on RNA expression and whether the mutation was inherited paternally or maternally.

RESULTS: Mutation carriers with loss of RNA expression (group 1) had a significantly lower age at CRC diagnosis (51.1 years vs. 60.0 years, P = 0.035) and a lower age at EC diagnosis (55.8 years vs. 61.0 years, P = 0.2, nonsignificant) compared with group 2 (retention of RNA expression). Furthermore, group 1 showed slightly higher, but nonsignificant, hazard ratios (HRs) for both CRC (HR: 1.31, P = 0.38) and EC (HR: 1.22, P = 0.72). No evidence for a significant parent-of-origin effect was found for either CRC or EC.

CONCLUSIONS: PMS2 mutation carriers with retention of RNA expression developed CRC 9 years later than those with loss of RNA expression. If confirmed, this finding would justify a delay in surveillance for these cases. Cancer risk was not influenced by a parent-of-origin effect.Genet Med advance online publication 25 June 2015Genetics in Medicine (2015); doi:10.1038/gim.2015.83.

OriginalsprogEngelsk
TidsskriftGenetics in Medicine
Vol/bind18
Udgave nummer4
Sider (fra-til)405-409
Antal sider5
ISSN1098-3600
DOI
StatusUdgivet - 2016

Bibliografisk note

Korrektion er udgivet:
Correction: Corrigendum: The effect of genotypes and parent of origin on cancer risk and age of cancer development in PMS2 mutation carriers.
Genetics in Medicine, Volume 18, Issue 1, s.108, 10.1038/gim.2015.178.

"In the published version of this article, author Hans J.J.P. Gille, from the Department of Clinical Genetics, VU Medical Centre, Amsterdam,
The Netherlands, was mistakenly omitted from the author list.
The affiliation listed for F.H. Menko, PhD was incorrect. The correct affiliation is the Department of Clinical Genetics, VU Medical Centre,
Amsterdam, The Netherlands.
The affiliation of Arjen Mensenkamp, PhD was incorrect. The correct affiliation is the Department of Clinical Genetics, Radboud University
Medical Centre, Nijmegen, The Netherlands.
The author name Maran Olderode was incomplete. The correct name is M.J.W. Olderode-Berends.
The authors regret these errors."

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