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Gut. 2017 Sep;66(9):1657-1664. doi: 10.1136/gutjnl-2016-311403. Epub 2016 Jun 3.

Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer: a report from the prospective Lynch syndrome database.

Author information

1
Research Group Inherited Cancer, Department of Medical Genetics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
2
Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Part of Oslo University Hospital, Oslo, Norway.
3
Surgical Center for Hereditary Tumors, HELIOS University Clinic Wuppertal, University Witten-Herdecke, Wuppertal, Germany.
4
Department of Surgery, Central Finland Health Care District, Jyväskylä, Finland.
5
The Danish Hereditary Non-polyposis Colorectal Cancer Register, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark.
6
Department Surgical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark.
7
Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.
8
MGZ-Medizinisch Genetisches Zentrum, Munich, Germany.
9
Unit of Hereditary Digestive Tract Tumors IRCCS, Istituto Nazionale Tumori, Milan, Italy.
10
Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
11
Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK.
12
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
13
Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
14
Department of Medicine, Melbourne University, Melbourne, Australia.
15
Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
16
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
17
Institute of Medical Genetics, Cardiff University School of Medicine, Cardiff, UK.
18
Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands.
19
Institute of Genetic Medicine Newcastle University, Newcastle upon Tyne, UK.
20
Institute of Cancer Genetics and Informatics, The Norwegian Radium Hospital, Part of Oslo University Hospital, Oslo, Norway.
21
Department of Informatics, University of Oslo, Oslo, Norway.
22
Department of Mathematics and Statistics, Lancaster University, Lancaster, UK.
23
Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, The Netherlands.
24
Department of Surgery, Central Manchester University Hospitals NHS Foundation Trust and University of Manchester, Manchester, UK.
25
Department of Clinical Genetics and Department of Human Genetics Leiden University Medical Centre, Leiden, The Netherlands.
26
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
27
Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
28
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
29
Division of Obstetrics and Gynecology, Department of Women's and Children's health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
30
Department of Surgery, Helsinki University Hospital, Helsinki, Finland.
31
Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland.
32
Department of Education and Science, Central Finland Health Care District, Jyväskylä, Finland.
33
Institute of Genomic Medicine, "A. Gemelli" Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
34
University of Eastern Finland, Jyvaskyla, Finland.

Abstract

OBJECTIVE:

Today most patients with Lynch syndrome (LS) survive their first cancer. There is limited information on the incidences and outcome of subsequent cancers. The present study addresses three questions: (i) what is the cumulative incidence of a subsequent cancer; (ii) in which organs do subsequent cancers occur; and (iii) what is the survival following these cancers?

DESIGN:

Information was collated on prospectively organised surveillance and prospectively observed outcomes in patients with LS who had cancer prior to inclusion and analysed by age, gender and genetic variants.

RESULTS:

1273 patients with LS from 10 countries were followed up for 7753 observation years. 318 patients (25.7%) developed 341 first subsequent cancers, including colorectal (n=147, 43%), upper GI, pancreas or bile duct (n=37, 11%) and urinary tract (n=32, 10%). The cumulative incidences for any subsequent cancer from age 40 to age 70 years were 73% for pathogenic MLH1 (path_MLH1), 76% for path_MSH2 carriers and 52% for path_MSH6 carriers, and for colorectal cancer (CRC) the cumulative incidences were 46%, 48% and 23%, respectively. Crude survival after any subsequent cancer was 82% (95% CI 76% to 87%) and 10-year crude survival after CRC was 91% (95% CI 83% to 95%).

CONCLUSIONS:

Relative incidence of subsequent cancer compared with incidence of first cancer was slightly but insignificantly higher than cancer incidence in patients with LS without previous cancer (range 0.94-1.49). The favourable survival after subsequent cancers validated continued follow-up to prevent death from cancer. The interactive website http://lscarisk.org was expanded to calculate the risks by gender, genetic variant and age for subsequent cancer for any patient with LS with previous cancer.

KEYWORDS:

CANCER GENETICS; COLORECTAL CANCER GENES; EPIDEMIOLOGY; INHERITED CANCERS; SCREENING

PMID:
27261338
PMCID:
PMC5561364
DOI:
10.1136/gutjnl-2016-311403
[Indexed for MEDLINE]
Free PMC Article

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