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

doi:10.1007/s10689-024-00357-4

. 2024 Jan 27.

doi: 10.1007/s10689-024-00357-4. Online ahead of print.

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

Sabine Biermann¹, Michael Knapp², Peter Wieacker³, Stefan Aretz^#^{4

5

6

7}, Verena Steinke-Lange^#^{8

9

10}

Affiliations

¹ Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany.
² Institut für Medizinische Biometrie, Informatik und Epidemiologie (IMBIE), University of Bonn, Bonn, Germany.
³ Institut für Humangenetik, Universität Münster, Münster, Germany.
⁴ Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany. stefan.aretz@uni-bonn.de.
⁵ National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany. stefan.aretz@uni-bonn.de.
⁶ European Reference Network for Genetic Tumor Risk Syndromes (ERN Genturis), Nijmegen, Netherlands. stefan.aretz@uni-bonn.de.
⁷ Institut für Humangenetik Biomedizinisches Zentrum, Venusberg-Campus 1, Bonn, 53127, Germany. stefan.aretz@uni-bonn.de.
⁸ European Reference Network for Genetic Tumor Risk Syndromes (ERN Genturis), Nijmegen, Netherlands.
⁹ MGZ - Medical Genetics Center, Munich, Germany.
¹⁰ Arbeitsgruppe erbliche gastrointestinale Tumore, Medizinische Klinik und Poliklinik IV - Campus Innenstadt, Klinikum der Universität München, Munich, Germany.

^# Contributed equally.

PMID: 38280980
DOI: 10.1007/s10689-024-00357-4

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

Sabine Biermann et al. Fam Cancer. 2024.

. 2024 Jan 27.

doi: 10.1007/s10689-024-00357-4. Online ahead of print.

Authors

Sabine Biermann¹, Michael Knapp², Peter Wieacker³, Stefan Aretz^#^{4

5

6

7}, Verena Steinke-Lange^#^{8

9

10}

Affiliations

¹ Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany.
² Institut für Medizinische Biometrie, Informatik und Epidemiologie (IMBIE), University of Bonn, Bonn, Germany.
³ Institut für Humangenetik, Universität Münster, Münster, Germany.
⁴ Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany. stefan.aretz@uni-bonn.de.
⁵ National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany. stefan.aretz@uni-bonn.de.
⁶ European Reference Network for Genetic Tumor Risk Syndromes (ERN Genturis), Nijmegen, Netherlands. stefan.aretz@uni-bonn.de.
⁷ Institut für Humangenetik Biomedizinisches Zentrum, Venusberg-Campus 1, Bonn, 53127, Germany. stefan.aretz@uni-bonn.de.
⁸ European Reference Network for Genetic Tumor Risk Syndromes (ERN Genturis), Nijmegen, Netherlands.
⁹ MGZ - Medical Genetics Center, Munich, Germany.
¹⁰ Arbeitsgruppe erbliche gastrointestinale Tumore, Medizinische Klinik und Poliklinik IV - Campus Innenstadt, Klinikum der Universität München, Munich, Germany.

^# Contributed equally.

PMID: 38280980
DOI: 10.1007/s10689-024-00357-4

Abstract

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.

Keywords: Cancer predisposition; Hereditary CRC; Lynch syndrome; Menopause; Mismatch-repair genes.

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References

1. 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 - PubMed - PMC
1. 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 - PubMed
1. 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 - PubMed
1. 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 - PubMed
1. Koch-Institut R DEGS – Studie zur Gesundheit Erwachsener in Deutschland. Projektbeschreibung. 118

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[1] 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 - PubMed - PMC

[2] 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 - PubMed - PMC

[3] 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 - PubMed

[4] 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 - PubMed

[5] 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 - PubMed

[6] 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 - PubMed

[7] 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 - PubMed

[8] 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 - PubMed

[9] Koch-Institut R DEGS – Studie zur Gesundheit Erwachsener in Deutschland. Projektbeschreibung. 118

[10] Koch-Institut R DEGS – Studie zur Gesundheit Erwachsener in Deutschland. Projektbeschreibung. 118

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

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

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