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Hered Cancer Clin Pract. 2019 Oct 14;17:28. doi: 10.1186/s13053-019-0127-3. eCollection 2019.

Survival by colon cancer stage and screening interval in Lynch syndrome: a prospective Lynch syndrome database report.

Author information

1
1Department of Tumor Biology, Institute of Cancer Research, Oslo University Hospital, Oslo, Norway.
2
2Department of Gastrointestinal Surgery, Helsinki University Central Hospital, Helsinki, Finland.
3
3Clinicum, University of Helsinki, Helsinki, Finland.
4
4Division of Cancer and Genetics, Institute of Medical Genetics, Cardiff University School of Medicine, Cardiff, UK.
5
5The Royal Melbourne Hospital, Melbourne, Australia.
6
6University of Melbourne, Melbourne, Australia.
7
7University of Manchester & Manchester University Hospitals Foundation Trust, Manchester, UK.
8
University of Newcastle and the Hunter Medical Research Institute, Callaghan, Australia.
9
9University of Newcastle, Newcastle upon Tyne, UK.
10
10University Witten-Herdecke, Wuppertal, Germany.
11
11Department of Surgical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark.
12
12Central Finland Central Hospital, Education and Research, Jyväskylä, Finland.
13
13Research Programs Unit, Genome-Scale Biology, University of Helsinki, Helsinki, Finland.
14
14Karolinska Institutet, Stockholm, Sweden.
15
15St Mark's Hospital, Department of Surgery and Cancer, Imperial College London, London, UK.
16
16University of Manchester and St Mary's Hospital, Manchester, UK.
17
17Hereditary Cancer Program, Catalan Institute of Oncology, Insititut d'Investigació Biomèdica de Bellvitge (IDIBELL), ONCOBELL Program, L'Hospitalet de Llobregat, Barcelona, Spain.
18
18Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
19
19Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark.
20
20Department of Surgery, Regional Hospital West Jutland, Egtved, Denmark.
21
21Department of Oncology, Aalborg University Hospital, Aalborg, Denmark.
22
22Department of Pathology, Herlev Gentofte University Hospital, Herlev, Denmark.
23
23High Risk and GI Cancer prevention Clinic, Gatro-Oncology Unit, The Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel.
24
24Leids Universitair Medisch Centrum, Leiden, Netherlands.
25
25Center for Bioinformatics, Department of Informatics, University of Oslo, Oslo, Norway.
26
26Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
27
27Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
28
28Cooperation Unit Applied Tumor Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
29
29Department of Health Sciences Research, Mayo Clinic, Scottsdale, AZ USA.
30
30Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.
31
31MGZ- Medical Genetics Center, Munich, Germany.
32
32Department of Surgery, Central Finland Central Hospital, Jyväskylä, Finland.
33
33Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
#
Contributed equally

Abstract

Background:

We previously reported that in pathogenic mismatch repair (path_MMR) variant carriers, the incidence of colorectal cancer (CRC) was not reduced when colonoscopy was undertaken more frequently than once every 3 years, and that CRC stage and interval since last colonoscopy were not correlated.

Methods:

The Prospective Lynch Syndrome Database (PLSD) that records outcomes of surveillance was examined to determine survival after colon cancer in relation to the time since previous colonoscopy and pathological stage. Only path_MMR variants scored by the InSiGHT variant database as class 4 or 5 (clinically actionable) were included in the analysis.

Results:

Ninety-nine path_MMR carriers had no cancer prior to or at first colonoscopy, but subsequently developed colon cancer. Among these, 96 were 65 years of age or younger at diagnosis, and included 77 path_MLH1, 17 path_MSH2, and 2 path_MSH6 carriers. The number of cancers detected within < 1.5, 1.5-2.5, 2.5-3.5 and at > 3.5 years after previous colonoscopy were 9, 43, 31 and 13, respectively. Of these, 2, 8, 4 and 3 were stage III, respectively, and only one stage IV (interval 2.5-3.5 years) disease. Ten-year crude survival after colon cancer were 93, 94 and 82% for stage I, II and III disease, respectively (p < 0.001). Ten-year crude survival when the last colonoscopy had been < 1.5, 1.5-2.5, 2.5-3.5 or > 3.5 years before diagnosis, was 89, 90, 90 and 92%, respectively (p = 0.91).

Conclusions:

In path_MLH1 and path_MSH2 carriers, more advanced colon cancer stage was associated with poorer survival, whereas time since previous colonoscopy was not. Although the numbers are limited, together with our previously reported findings, these results may be in conflict with the view that follow-up of path_MMR variant carriers with colonoscopy intervals of less than 3 years provides significant benefit.

KEYWORDS:

Cancer stage; Colon cancer; Colonoscopy; Lynch syndrome; Surveillance; Survival

Conflict of interest statement

Competing interestsToni Seppälä: a co-owner (20%) of Healthfund Finland Oy (educational and health care services in Finland, not related to patients or scope of this manuscript). Travel costs to a scientific meeting by Medtronic Finland. John Burn: a patent for high speed low cost tumor profiling pending to John Burn and QuantuMDx. All others: None declared.

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