Observational Study

. 2020 Jan;22(1):15-25.

doi: 10.1038/s41436-019-0596-9. Epub 2019 Jul 24.

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

Mev Dominguez-Valentin^#¹, Julian R Sampson^#², Toni T Seppälä^#^{3

4}, Sanne W Ten Broeke⁵, John-Paul Plazzer⁶, Sigve Nakken⁷, Christoph Engel⁸, Stefan Aretz⁹, Mark A Jenkins¹⁰, Lone Sunde^{11

12}, Inge Bernstein¹³, Gabriel Capella¹⁴, Francesc Balaguer¹⁵, Huw Thomas¹⁶, D Gareth Evans^{17

18}, John Burn¹⁹, Marc Greenblatt²⁰, Eivind Hovig^{7

21}, Wouter H de Vos Tot Nederveen Cappel²², Rolf H Sijmons²³, Lucio Bertario²⁴, Maria Grazia Tibiletti²⁵, Giulia Martina Cavestro²⁶, Annika Lindblom²⁷, Adriana Della Valle²⁸, Francisco Lopez-Köstner²⁹, Nathan Gluck³⁰, Lior H Katz³¹, Karl Heinimann³², Carlos A Vaccaro^{33

34}, Reinhard Büttner³⁵, Heike Görgens³⁶, Elke Holinski-Feder^{37

38}, Monika Morak^{37

38}, Stefanie Holzapfel⁹, Robert Hüneburg³⁹, Magnus von Knebel Doeberitz^{40

41}, Markus Loeffler⁸, Nils Rahner⁴², Hans K Schackert³⁶, Verena Steinke-Lange^{37

38}, Wolff Schmiegel⁴³, Deepak Vangala⁴³, Kirsi Pylvänäinen⁴⁴, Laura Renkonen-Sinisalo^{45

46}, John L Hopper¹⁰, Aung Ko Win¹⁰, Robert W Haile⁴⁷, Noralane M Lindor⁴⁸, Steven Gallinger⁴⁹, Loïc Le Marchand⁵⁰, Polly A Newcomb⁵¹, Jane C Figueiredo⁵², Stephen N Thibodeau⁵³, Karin Wadt⁵⁴, Christina Therkildsen⁵⁵, Henrik Okkels⁵⁶, Zohreh Ketabi⁵⁷, Leticia Moreira¹⁵, Ariadna Sánchez¹⁵, Miquel Serra-Burriel⁵⁸, Marta Pineda⁵⁹, Matilde Navarro⁵⁹, Ignacio Blanco⁵⁹, Kate Green¹⁷, Fiona Lalloo¹⁷, Emma J Crosbie⁶⁰, James Hill⁶¹, Oliver G Denton⁶², Ian M Frayling⁶², Einar Andreas Rødland⁷, Hans Vasen⁶³, Miriam Mints⁶⁴, Florencia Neffa²⁸, Patricia Esperon²⁸, Karin Alvarez²⁹, Revital Kariv³⁰, Guy Rosner³⁰, Tamara Alejandra Pinero^{33

34}, María Laura Gonzalez³³, Pablo Kalfayan³³, Douglas Tjandra⁶⁵, Ingrid M Winship^{65

66}, Finlay Macrae^{6

65}, Gabriela Möslein⁶⁷, Jukka-Pekka Mecklin⁶⁸, Maartje Nielsen⁵, Pål Møller^{7

69

70}

Affiliations

¹ Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. mev.dominguez.valentin@rr-research.no.
² Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK. sampson@cardiff.ac.uk.
³ Department of Gastrointestinal Surgery, Helsinki University Central Hospital, Helsinki, Finland. toni.seppala@fimnet.fi.
⁴ Clinicum, University of Helsinki, Helsinki, Finland. toni.seppala@fimnet.fi.
⁵ Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
⁶ Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Australia.
⁷ Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
⁸ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
⁹ Institute of Human Genetics, University of Bonn, Bonn, Germany.
¹⁰ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia.
¹¹ Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
¹² Department of Biomedicine, Aarhus University, Aarhus, Denmark.
¹³ Department of Surgical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark.
¹⁴ Hereditary Cancer Program, Institut Catal. d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
¹⁵ Gastroenterology Department, Hospital Clinic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
¹⁶ St Mark's Hospital, Department of Surgery and Cancer, Imperial College London, London, UK.
¹⁷ Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
¹⁸ Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK.
¹⁹ Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
²⁰ University of Vermont College of Medicine, Burlington, VT, USA.
²¹ Institute of Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
²² Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, The Netherlands.
²³ Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
²⁴ Unit of Hereditary Digestive Tract Tumors IRCCS Istituto Nazionale Tumori and Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy.
²⁵ Ospedale di Circolo ASST Settelaghi, Centro di Ricerca tumori eredo-familiari, Università dell'Insubria, Varese, Italy.
²⁶ Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy.
²⁷ Department of Molecular Medicine and Surgery and Department of Clinical Genetics, Karolinska Institutet and University Hospital, Stockholm, Sweden.
²⁸ Hospital Fuerzas Armadas, Grupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU), Montevideo, Uruguay.
²⁹ Lab. Oncología y Genética Molecular, Unidad de coloproctología, Clínica Las Condes, Santiago, Chile.
³⁰ Department of Gastroenterology, Tel Aviv Sourasky Medical Centre and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
³¹ High Risk and GI Cancer prevention Clinic, Gastro-Oncology Unit, The Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel.
³² Institute for Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
³³ Hereditary Cancer Program (PROCANHE), Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
³⁴ Instituto de Medicina Traslacional e Ingenieria Biomedica (IMTIB), CONICET IU, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
³⁵ Institute of Pathology, University of Cologne, Cologne, Germany.
³⁶ Department of Surgical Research, Technische Universität Dresden, Dresden, Germany.
³⁷ Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.
³⁸ Center of Medical Genetics, Munich, Germany.
³⁹ Department of Internal Medicine, University Hospital Bonn, Bonn, Germany.
⁴⁰ Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
⁴¹ Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁴² Institute of Human Genetics, Medical School, Heinrich-Heine-University, Dusseldorf, Germany.
⁴³ Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.
⁴⁴ Department of Education and Science, Central Finland Health Care District, Jyväskylä, Finland.
⁴⁵ Department of Gastrointestinal Surgery, Helsinki University Central Hospital, Helsinki, Finland.
⁴⁶ Applied Tumour Genomics Research Program, University of Helsinki, Helsinki, Finland.
⁴⁷ Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, Palo Alto, CA, USA.
⁴⁸ Department of Health Science Research, Mayo Clinic Arizona, Phoenix, AZ, USA.
⁴⁹ Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
⁵⁰ University of Hawaii Cancer Center, Honolulu, HI, USA.
⁵¹ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
⁵² Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁵³ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
⁵⁴ Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark.
⁵⁵ The Danish HNPCC Register, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark.
⁵⁶ Department of Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark.
⁵⁷ Department of Obstetrics and Gynaecology, Copenhagen University Hospital, Rigshospitalet, Denmark.
⁵⁸ Universitat de Barcelona & Centre de Recerca en Economia i Salut (CRES-UPF), Barcelona, Spain.
⁵⁹ Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
⁶⁰ Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester and St Mary's Hospital, Manchester, UK.
⁶¹ Department of Surgery, Central Manchester University Hospitals NHS Foundation Trust and University of Manchester, Manchester, UK.
⁶² Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK.
⁶³ Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands.
⁶⁴ Department of Women's and Children's health, Division of Obstetrics and Gyneacology, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden.
⁶⁵ Department of Medicine, Melbourne University, Melbourne, Australia.
⁶⁶ Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia.
⁶⁷ Surgical Center for Hereditary Tumors, HELIOS University Clinic Wuppertal, University of Witten-Hardecke, Wuppertal, Germany.
⁶⁸ Departments of Surgery, University of Jyväskylä and Central Finland Central Hospital, Jyväskylä, Finland.
⁶⁹ Department of Medical Genetics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
⁷⁰ Centre for Cancer Cell Reprogamming, University of Oslo, Oslo, Norway.

^# Contributed equally.

PMID: 31337882
PMCID: PMC7371626
DOI: 10.1038/s41436-019-0596-9

Observational Study

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

Mev Dominguez-Valentin et al. Genet Med. 2020 Jan.

. 2020 Jan;22(1):15-25.

doi: 10.1038/s41436-019-0596-9. Epub 2019 Jul 24.

Authors

Affiliations

¹ Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. mev.dominguez.valentin@rr-research.no.
² Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK. sampson@cardiff.ac.uk.
³ Department of Gastrointestinal Surgery, Helsinki University Central Hospital, Helsinki, Finland. toni.seppala@fimnet.fi.
⁴ Clinicum, University of Helsinki, Helsinki, Finland. toni.seppala@fimnet.fi.
⁵ Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
⁶ Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Australia.
⁷ Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
⁸ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
⁹ Institute of Human Genetics, University of Bonn, Bonn, Germany.
¹⁰ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia.
¹¹ Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
¹² Department of Biomedicine, Aarhus University, Aarhus, Denmark.
¹³ Department of Surgical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark.
¹⁴ Hereditary Cancer Program, Institut Catal. d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
¹⁵ Gastroenterology Department, Hospital Clinic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
¹⁶ St Mark's Hospital, Department of Surgery and Cancer, Imperial College London, London, UK.
¹⁷ Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
¹⁸ Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK.
¹⁹ Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
²⁰ University of Vermont College of Medicine, Burlington, VT, USA.
²¹ Institute of Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
²² Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, The Netherlands.
²³ Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
²⁴ Unit of Hereditary Digestive Tract Tumors IRCCS Istituto Nazionale Tumori and Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy.
²⁵ Ospedale di Circolo ASST Settelaghi, Centro di Ricerca tumori eredo-familiari, Università dell'Insubria, Varese, Italy.
²⁶ Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy.
²⁷ Department of Molecular Medicine and Surgery and Department of Clinical Genetics, Karolinska Institutet and University Hospital, Stockholm, Sweden.
²⁸ Hospital Fuerzas Armadas, Grupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU), Montevideo, Uruguay.
²⁹ Lab. Oncología y Genética Molecular, Unidad de coloproctología, Clínica Las Condes, Santiago, Chile.
³⁰ Department of Gastroenterology, Tel Aviv Sourasky Medical Centre and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
³¹ High Risk and GI Cancer prevention Clinic, Gastro-Oncology Unit, The Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel.
³² Institute for Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
³³ Hereditary Cancer Program (PROCANHE), Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
³⁴ Instituto de Medicina Traslacional e Ingenieria Biomedica (IMTIB), CONICET IU, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
³⁵ Institute of Pathology, University of Cologne, Cologne, Germany.
³⁶ Department of Surgical Research, Technische Universität Dresden, Dresden, Germany.
³⁷ Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.
³⁸ Center of Medical Genetics, Munich, Germany.
³⁹ Department of Internal Medicine, University Hospital Bonn, Bonn, Germany.
⁴⁰ Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
⁴¹ Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁴² Institute of Human Genetics, Medical School, Heinrich-Heine-University, Dusseldorf, Germany.
⁴³ Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.
⁴⁴ Department of Education and Science, Central Finland Health Care District, Jyväskylä, Finland.
⁴⁵ Department of Gastrointestinal Surgery, Helsinki University Central Hospital, Helsinki, Finland.
⁴⁶ Applied Tumour Genomics Research Program, University of Helsinki, Helsinki, Finland.
⁴⁷ Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, Palo Alto, CA, USA.
⁴⁸ Department of Health Science Research, Mayo Clinic Arizona, Phoenix, AZ, USA.
⁴⁹ Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
⁵⁰ University of Hawaii Cancer Center, Honolulu, HI, USA.
⁵¹ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
⁵² Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁵³ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
⁵⁴ Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark.
⁵⁵ The Danish HNPCC Register, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark.
⁵⁶ Department of Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark.
⁵⁷ Department of Obstetrics and Gynaecology, Copenhagen University Hospital, Rigshospitalet, Denmark.
⁵⁸ Universitat de Barcelona & Centre de Recerca en Economia i Salut (CRES-UPF), Barcelona, Spain.
⁵⁹ Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
⁶⁰ Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester and St Mary's Hospital, Manchester, UK.
⁶¹ Department of Surgery, Central Manchester University Hospitals NHS Foundation Trust and University of Manchester, Manchester, UK.
⁶² Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK.
⁶³ Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands.
⁶⁴ Department of Women's and Children's health, Division of Obstetrics and Gyneacology, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden.
⁶⁵ Department of Medicine, Melbourne University, Melbourne, Australia.
⁶⁶ Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Australia.
⁶⁷ Surgical Center for Hereditary Tumors, HELIOS University Clinic Wuppertal, University of Witten-Hardecke, Wuppertal, Germany.
⁶⁸ Departments of Surgery, University of Jyväskylä and Central Finland Central Hospital, Jyväskylä, Finland.
⁶⁹ Department of Medical Genetics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
⁷⁰ Centre for Cancer Cell Reprogamming, University of Oslo, Oslo, Norway.

^# Contributed equally.

PMID: 31337882
PMCID: PMC7371626
DOI: 10.1038/s41436-019-0596-9

Erratum in

Correction: Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database.
Dominguez-Valentin M, Sampson JR, Seppälä TT, Ten Broeke SW, Plazzer JP, Nakken S, Engel C, Aretz S, Jenkins MA, Sunde L, Bernstein I, Capella G, Balaguer F, Thomas H, Evans DG, Burn J, Greenblatt M, Hovig E, de Vos Tot Nederveen Cappel WH, Sijmons RH, Bertario L, Tibiletti MG, Cavestro GM, Lindblom A, Della Valle A, Lopez-Köstner F, Gluck N, Katz LH, Heinimann K, Vaccaro CA, Büttner R, Görgens H, Holinski-Feder E, Morak M, Holzapfel S, Hüneburg R, Knebel Doeberitz MV, Loeffler M, Rahner N, Schackert HK, Steinke-Lange V, Schmiegel W, Vangala D, Pylvänäinen K, Renkonen-Sinisalo L, Hopper JL, Win AK, Haile RW, Lindor NM, Gallinger S, Le Marchand L, Newcomb PA, Figueiredo JC, Thibodeau SN, Wadt K, Therkildsen C, Okkels H, Ketabi Z, Moreira L, Sánchez A, Serra-Burriel M, Pineda M, Navarro M, Blanco I, Green K, Lalloo F, Crosbie EJ, Hill J, Denton OG, Frayling IM, Rødland EA, Vasen H, Mints M, Neffa F, Esperon P, Alvarez K, Kariv R, Rosner G, Pinero TA, Gonzalez ML, Kalfayan P, Tjandra D, Winship IM, Macrae F, Möslein G, Mecklin JP, Nielsen M, Møller P. Dominguez-Valentin M, et al. Genet Med. 2020 Sep;22(9):1569. doi: 10.1038/s41436-020-0892-4. Genet Med. 2020. PMID: 32690931 Free PMC article.

Abstract

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.

Keywords: Lynch syndrome; MLH1; MSH2; MSH6; PMS2.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

**Fig. 1**
**Cummulative risk of any cancer and of colorectal cancer in orginal and validation cohorts.** Cumulative risk of any cancer: a original cohort, b validation cohort; and cumulative risk of colorectal cancer (CRC): c original cohort and d validation cohort. There were no significant differences between original and validation cohorts. Center values are means and error bars show 95% confidence intervals (CIs).

**Fig. 2**
Age and sex of patients at inclusion in the Prospective Lynch Syndrome Database (PLSD).

**Fig. 3**
**Cumulative risk for any cancer (penetrance) of** ***path_MMR*** **gene variants causing Lynch syndrome by gender.** a cumulative risk of any cancer for each LS gene in males, b cumulative risk of any cancer for each LS gene in females. *Path_MSH6* had significantly higher penetrance in females compared with males. Center values are means and error bars show 95% confidence intervals (CIs).

See this image and copyright information in PMC

Comment in

Response to Tolva et al.
Sampson JR, Dominguez-Valentin M, Seppälä TT, Møller P. Sampson JR, et al. Genet Med. 2020 Apr;22(4):813-814. doi: 10.1038/s41436-019-0717-5. Epub 2019 Dec 5. Genet Med. 2020. PMID: 31801985 No abstract available.
Response to Dominguez-Valentin M et al. 2019: Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database.
Tolva G, Gandini S, Marabelli M, Calvello M, Guerrieri-Gonzaga A, Bertario L, Bonanni B. Tolva G, et al. Genet Med. 2020 Apr;22(4):811-812. doi: 10.1038/s41436-019-0716-6. Epub 2019 Dec 5. Genet Med. 2020. PMID: 31831884 No abstract available.
Correspondence on "Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database" by Dominguez-Valentin et al.
Chambuso R, Kaambo E, Rebello G, Ramesar R. Chambuso R, et al. Genet Med. 2022 May;24(5):1148-1150. doi: 10.1016/j.gim.2022.01.006. Epub 2022 Feb 12. Genet Med. 2022. PMID: 35168886 No abstract available.
Response to Chambuso et al.
Dominguez-Valentin M, Sampson JR, Seppälä TT, Møller P. Dominguez-Valentin M, et al. Genet Med. 2022 May;24(5):1151. doi: 10.1016/j.gim.2022.01.005. Epub 2022 Feb 23. Genet Med. 2022. PMID: 35216900 No abstract available.

References

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

Affiliations

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

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

Comment in

References

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Full Text Sources

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Medical

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