TY  - JOUR
A1  - Seppälä, Toni T.
A1  - Ahadova, Aysel
A1  - Dominguez-Valentin, Mev
A1  - Macrae, Finlay
A1  - Evans, D. Gareth
A1  - Therkildsen, Christina
A1  - Sampson, Julian
A1  - Scott, Rodney
A1  - Burn, John
A1  - Möslein, Gabriela
A1  - Bernstein, Inge
A1  - Holinski-Feder, Elke
A1  - Pylvänäinen, Kirsi
A1  - Renkonen-Sinisalo, Laura
A1  - Lepistö, Anna
A1  - Lautrup, Charlotte Kvist
A1  - Lindblom, Annika
A1  - Plazzer, John-Paul
A1  - Winship, Ingrid
A1  - Tjandra, Douglas
A1  - Katz, Lior H.
A1  - Aretz, Stefan
A1  - Hüneburg, Robert
A1  - Holzapfel, Stefanie
A1  - Heinimann, Karl
A1  - Della Valle, Adriana
A1  - Neffa, Florencia
A1  - Gluck, Nathan
A1  - de Vos tot Nederveen Cappel, Wouter H.
A1  - Vasen, Hans
A1  - Morak, Monika
A1  - Steinke-Lange, Verena
A1  - Engel, Christoph
A1  - Rahner, Nils
A1  - Schmiegel, Wolff
A1  - Vangala, Deepak
A1  - Thomas, Huw
A1  - Green, Kate
A1  - Lalloo, Fiona
A1  - Crosbie, Emma J.
A1  - Hill, James
A1  - Capella, Gabriel
A1  - Pineda, Marta
A1  - Navarro, Matilde
A1  - Blanco, Ignacio
A1  - ten Broeke, Sanne
A1  - Nielsen, Maartje
A1  - Ljungmann, Ken
A1  - Nakken, Sigve
A1  - Lindor, Noralane
A1  - Frayling, Ian
A1  - Hovig, Eivind
A1  - Sunde, Lone
A1  - Kloor, Matthias
A1  - Mecklin, Jukka-Pekka
A1  - Kalager, Mette
A1  - Møller, Pål
PB  - BioMed Central ; Springer
KW  - Mismatch repair
KW  -  Microsatellite instability
KW  -  Lynch syndrome
KW  -  Hereditary cancer
KW  -  Colorectal cancer
KW  -  Hereditary nonpolyposis colorectal cancer
KW  -  Colonoscopy
KW  -  Endoscopy
KW  -  Surveillance
KW  -  Screening
KW  -  Over-diagnosis
TI  - 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
SP  - 1
IS  - 8
N2  - 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.
VL  - 17
CY  - London ; Berlin, Heidelberg
AV  - public
Y1  - 2019///
EP  - 8
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/26147/
ID  - heidok26147
SN  - 1897-4287
JF  - Hereditary Cancer in Clinical Practice
ER  -