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

Autor: Suerink M; Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands., van der Klift HM; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands., Ten Broeke SW; Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands., Dekkers OM; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands., Bernstein I; Surgical Gastroenterology Department, Aalborg University Hospital, Aalborg, Denmark.; Danish HNPCC Registry, Copenhagen, Denmark., Capellá Munar G; Laboratori de Recerca Translacional, Catalan Institute of Oncology, Barcelona (ICO-IDIBELL), Spain., Gomez Garcia E; Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands., Hoogerbrugge N; Department of Clinical Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.; Department of Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands., Letteboer TG; Department of Clinical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands., Menko FH; Netherlands Cancer Institute, Amsterdam, The Netherlands., Lindblom A; Department of Clinical Genetics, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden.; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden., Mensenkamp A; Department of Clinical Genetics, VU Medical Centre, Amsterdam, The Netherlands., Moller P; Department of Medical Genetics, Research Group Inherited Cancer, Oslo University Hospital, Oslo, Norway., van Os TA; Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands., Rahner N; Institut für Humangenetik und Anthropologie, Dusseldorf, Germany., Redeker BJ; Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands., Olderode-Berends MJ, Spruijt L; Department of Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands., Vos YJ; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Wagner A; Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands., Morreau H; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands., Hes FJ; Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands., Vasen HF; Department of Gastroenterology, Leiden University Medical Center, Leiden, The Netherlands., Tops CM; Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands., Wijnen JT; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands., Nielsen M; Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Jazyk: angličtina
Zdroj: Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2016 Apr; Vol. 18 (4), pp. 405-9. Date of Electronic Publication: 2015 Jun 25.
DOI: 10.1038/gim.2015.83
Abstrakt: 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 18 4, 405-409.
Databáze: MEDLINE
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