High amount of fertility reducing tumors and procedures, but no evidence for premature ovarian failure in female Lynch syndrome patients.

Cancer predisposition Hereditary CRC Lynch syndrome Menopause Mismatch-repair genes

Journal

Familial cancer
ISSN: 1573-7292
Titre abrégé: Fam Cancer
Pays: Netherlands
ID NLM: 100898211

Informations de publication

Date de publication:
27 Jan 2024
Historique:
received: 11 12 2023
accepted: 14 01 2024
medline: 28 1 2024
pubmed: 28 1 2024
entrez: 27 1 2024
Statut: aheadofprint

Résumé

Lynch syndrome (LS; HNPCC) patients carry heterozygous pathogenic germline variants in mismatch repair (MMR) genes, which have also been shown to play an important role in meiosis. Therefore, it was hypothesized, that LS might be associated with a higher risk for premature ovarian failure (POF) or earlier menopause. Data on medical gynaecological history, cancer diagnoses and therapy were collected from 167 female LS patients and compared to a population-based control cohort. There was no difference between the age of menopause in patients compared to controls and no evidence for a higher risk of POF in LS patients. However, around one third (35%) of the probands have already had premenopausal cancer and mostly cancer-related treatment affecting fertility before the age of 45 years. Therefore, childbearing time might still be limited in these patients, especially due to the premenopausal cancer risk. LS patients should be informed in time about the elevated premenopausal cancer risks and the possible impact on family planning. This is particularly relevant since the average childbearing age has increased during the last decades.

Identifiants

pubmed: 38280980
doi: 10.1007/s10689-024-00357-4
pii: 10.1007/s10689-024-00357-4
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s).

Références

Beck-Peccoz P, Persani L (2006) Premature ovarian failure. Orphanet J Rare Dis 1:9. https://doi.org/10.1186/1750-1172-1-9
doi: 10.1186/1750-1172-1-9 pubmed: 16722528 pmcid: 1502130
Lipkin SM, Moens PB, Wang V et al (2002) Meiotic arrest and aneuploidy in MLH3-deficient mice. Nat Genet 31:385–390. https://doi.org/10.1038/ng931
doi: 10.1038/ng931 pubmed: 12091911
Dominguez-Valentin M, Sampson JR, Seppälä TT et al (2020) Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the prospective Lynch Syndrome Database. Genet Med 22:15–25. https://doi.org/10.1038/s41436-019-0596-9
doi: 10.1038/s41436-019-0596-9 pubmed: 31337882
Mangold E, Pagenstecher C, Friedl W et al (2005) Spectrum and frequencies of mutations in MSH2 and MLH1 identified in 1,721 German families suspected of hereditary nonpolyposis colorectal cancer. Int J Cancer 116:692–702. https://doi.org/10.1002/ijc.20863
doi: 10.1002/ijc.20863 pubmed: 15849733
Koch-Institut R DEGS – Studie zur Gesundheit Erwachsener in Deutschland. Projektbeschreibung. 118
Avdievich E, Reiss C, Scherer SJ et al (2008) Distinct effects of the recurrent Mlh1G67R mutation on MMR functions, cancer, and meiosis. Proc Natl Acad Sci U S A 105:4247–4252. https://doi.org/10.1073/pnas.0800276105
doi: 10.1073/pnas.0800276105 pubmed: 18337503 pmcid: 2393764
Edelmann W, Cohen PE, Kneitz B et al (1999) Mammalian MutS homologue 5 is required for chromosome pairing in meiosis. Nat Genet 21:123–127. https://doi.org/10.1038/5075
doi: 10.1038/5075 pubmed: 9916805
Mandon-Pépin B, Touraine P, Kuttenn F et al (2008) Genetic investigation of four meiotic genes in women with premature ovarian failure. Eur J Endocrinol 158:107–115. https://doi.org/10.1530/EJE-07-0400
doi: 10.1530/EJE-07-0400 pubmed: 18166824
Statistisches Bundesamt - Daten zum durchschnittlichen Alter der Mutter bei Geburt insgesamt und 1. Kind nach Bundesländern. https://www.destatis.de/DE/Themen/Gesellschaft-Umwelt/Bevoelkerung/Geburten/Tabellen/geburten-mutter-alter-bundeslaender.html jsessionid=5432BDEDF843D7F3824A2EEEE9AF9CAC.live732?view=main[Print]. Accessed 18 May 2021

Auteurs

Sabine Biermann (S)

Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany.

Michael Knapp (M)

Institut für Medizinische Biometrie, Informatik und Epidemiologie (IMBIE), University of Bonn, Bonn, Germany.

Peter Wieacker (P)

Institut für Humangenetik, Universität Münster, Münster, Germany.

Stefan Aretz (S)

Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany. stefan.aretz@uni-bonn.de.
National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany. stefan.aretz@uni-bonn.de.
European Reference Network for Genetic Tumor Risk Syndromes (ERN Genturis), Nijmegen, Netherlands. stefan.aretz@uni-bonn.de.
Institut für Humangenetik Biomedizinisches Zentrum, Venusberg-Campus 1, Bonn, 53127, Germany. stefan.aretz@uni-bonn.de.

Verena Steinke-Lange (V)

European Reference Network for Genetic Tumor Risk Syndromes (ERN Genturis), Nijmegen, Netherlands.
MGZ - Medical Genetics Center, Munich, Germany.
Arbeitsgruppe erbliche gastrointestinale Tumore, Medizinische Klinik und Poliklinik IV - Campus Innenstadt, Klinikum der Universität München, Munich, Germany.

Classifications MeSH