- Title
- Lack of association between screening interval and cancer stage in Lynch syndrome may be accounted for by over-diagnosis; a prospective Lynch syndrome database report
- Creator
- Seppala, Toni T.; Ahadova, Aysel; Bernstein, Inge; Holinski-Feder, Elke; Pylvanainen, Kirsi; Renkonen-Sinisalo, Laura; Lepisto, Anna; Lautrup, Charlotte Kvist; Lindblom, Annika; Plazzer, John-Paul; Winship, Ingrid; Tjandra, Douglas; Dominguez-Valentin, Mev; Katz, Lior H.; Aretz, S; Hueneburg, R; Holzapfel, S; Heinimann, K; Della Valle, A; Neffa, F; Gluck, N; Cappel, WHDVTN; Vasen, H; Macrae, Finlay; Morak, M; Steinke-Lange, V; Engel, C; Rahner, N; Schmiegel, W; Vangala, D; Thomas, H; Green, K; Lalloo, F; Crosbie, EJ; Evans, D. Gareth; Hill, J; Capella, G; Pineda, M; Navarro, M; Blanco, I; ten Broeke, S; Nielsen, M; Ljungmann, K; Nakken, S; Lindor, N; Therkildsen, Christina; Frayling, I; Hovig, E; Sunde, L; Kloor, M; Mecklin, J-P; Kalager, M; Moller, P; Sampson, Julian; Scott, Rodney; Burn, John; Moeslein, Gabriela
- Relation
- Hereditary Cancer in Clinical Practice Vol. 17, no. 8
- Publisher Link
- http://dx.doi.org/10.1186/s13053-019-0106-8
- Publisher
- BioMed Central
- Resource Type
- journal article
- Date
- 2019
- Description
- Background: Recent epidemiological evidence shows that colorectal cancer (CRC) continues to occur in carriers of pathogenic mismatch repair (path_MMR) variants despite frequent colonoscopy surveillance in expert centres. This observation conflicts with the paradigm that removal of all visible polyps should prevent the vast majority of CRC in path_MMR carriers, provided the screening interval is sufficiently short and colonoscopic practice is optimal. Methods: To inform the debate, we examined, in the Prospective Lynch Syndrome Database (PLSD), whether the time since last colonoscopy was associated with the pathological stage at which CRC was diagnosed during prospective surveillance. Path_MMR carriers were recruited for prospective surveillance by colonoscopy. Only variants scored by the InSiGHT Variant Interpretation Committee as class 4 and 5 (clinically actionable) were included. CRCs detected at the first planned colonoscopy, or within one year of this, were excluded as prevalent cancers. Results: Stage at diagnosis and interval between last prospective surveillance colonoscopy and diagnosis were available for 209 patients with 218 CRCs, including 162 path_MLH1, 45 path_MSH2, 10 path_MSH6 and 1 path_PMS2 carriers. The numbers of cancers detected within < 1.5, 1.5–2.5, 2.5–3.5 and at > 3.5 years since last colonoscopy were 36, 93, 56 and 33, respectively. Among these, 16.7, 19.4, 9.9 and 15.1% were stage III–IV, respectively (p = 0.34). The cancers detected more than 2.5 years after the last colonoscopy were not more advanced than those diagnosed earlier (p = 0.14). Conclusions: The CRC stage and interval since last colonoscopy were not correlated, which is in conflict with the accelerated adenoma-carcinoma paradigm. We have previously reported that more frequent colonoscopy is not associated with lower incidence of CRC in path_MMR carriers as was expected. In contrast, point estimates showed a higher incidence with shorter intervals between examinations, a situation that may parallel to over-diagnosis in breast cancer screening. Our findings raise the possibility that some CRCs in path_MMR carriers may spontaneously disappear: the host immune response may not only remove CRC precursor lesions in path_MMR carriers, but may remove infiltrating cancers as well. If confirmed, our suggested interpretation will have a bearing on surveillance policy for path_MMR carriers.
- Subject
- mismatch repair; miscrosatellite instability; over-diagnosis; SDG 3; Sustainable Development Goals; Lynch syndrome; hereditary cancer; colorectal cancer; hereditary nonpolyposis colorectal cancer; colonoscopy; endoscopy; surveillance; screening
- Identifier
- http://hdl.handle.net/1959.13/1455532
- Identifier
- uon:45110
- Identifier
- ISSN:1731-2302
- Rights
- This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Language
- eng
- Full Text
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