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
Seppälä, T. T., Ahadova, A., Dominguez-Valentin, M., Macrae, F., Evans, D. G., Therkildsen, C., Sampson, J., Scott, R., Burn, J., Möslein, G., Bernstein, I., Holinski-Feder, E., Pylvänäinen, K., Renkonen-Sinisalo, L., Lepistö, A., Lautrup, C. K., Lindblom, A., Plazzer, J.-P., Winship, I., . . . Møller, P. (2019). 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. Hereditary Cancer in Clinical Practice, 17, Article 8. https://doi.org/10.1186/s13053-019-0106-8
Published inHereditary Cancer in Clinical Practice
© The Author(s). 2019
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. ...
PublisherBioMed Central Ltd.
ISSN Search the Publication Forum1731-2302
tähystys colonoscopy colorectal cancer hereditary cancer hereditary nonpolyposis colorectal cancer microsatellite instability mismatch repair over-diagnosis screening syöpätaudit perinnölliset taudit suolistosyövät Lynchin oireyhtymä diagnostiikka seulontatutkimus endoskopia koloskopia DNA mikrosatelliitit tarkkailu
Publication in research information system
MetadataShow full item record
- Liikuntatieteiden tiedekunta 
Showing items with similar title or keywords.
The “unnatural” history of colorectal cancer in Lynch syndrome : lessons from colonoscopy surveillance Ahadova, Aysel; Seppälä, Toni T.; Engel, Christoph; Gallon, Richard; Burn, John; Holinski‐Feder, Elke; Steinke‐Lange, Verena; Möslein, Gabriela; Nielsen, Maartje; ten Broeke, Sanne; Laghi, Luigi; Dominguez‐Valentin, Mev; Capella, Gabriel; Macrae, Finlay; Scott, Rodney; Hüneburg, Robert; Nattermann, Jacob; Hoffmeister, Michael; Brenner, Hermann; Bläker, Hendrik; von Knebel Doeberit,z Magnus; Sampson, Julian R.; Vasen, Hans; Mecklin, Jukka‐Pekka; Møller, Pål; Kloor, Matthias (Wiley, 2021)Individuals with Lynch syndrome (LS), one of the most common inherited cancer syndromes, are at increased risk of developing malignancies, in particular colorectal cancer (CRC). Regular colonoscopy with polypectomy is ...
Distinct Mutational Profile of Lynch Syndrome Colorectal Cancers Diagnosed under Regular Colonoscopy Surveillance Ahadova, Aysel; Pfuderer, Pauline Luise; Ahtiainen, Maarit; Ballhausen, Alexej; Bohaumilitzky, Lena; Kösegi, Svenja; Müller, Nico; Tang, Yee Lin; Kosmalla, Kosima; Witt, Johannes; Endris, Volker; Stenzinger, Albrecht; von Knebel Doeberitz, Magnus; Bläker, Hendrik; Renkonen-Sinisalo, Laura; Lepistö, Anna; Böhm, Jan; Mecklin, Jukka-Pekka; Seppälä, Toni T.; Kloor, Matthias (MDPI AG, 2021)Regular colonoscopy even with short intervals does not prevent all colorectal cancers (CRC) in Lynch syndrome (LS). In the present study, we asked whether cancers detected under regular colonoscopy surveillance (incident ...
Body Weight, Physical Activity, and Risk of Cancer in Lynch Syndrome Sievänen, Tero; Törmäkangas, Timo; Laakkonen, Eija K.; Mecklin, Jukka-Pekka; Pylvänäinen, Kirsi; Seppälä, Toni T.; Peltomäki, Päivi; Sipilä, Sarianna; Sillanpää, Elina (MDPI AG, 2021)Lynch syndrome (LS) increases cancer risk. There is considerable individual variation in LS cancer occurrence, which may be moderated by lifestyle factors, such as body weight and physical activity (PA). The potential ...
Colorectal cancer incidences in Lynch syndrome : a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium Møller, Pål; Seppälä, Toni; Dowty, James G.; Haupt, Saskia; Dominguez-Valentin, Mev; Sunde, Lone; Bernstein, Inge; Engel, Christoph; Aretz, Stefan; Nielsen, Maartje; Capella, Gabriel; Evans, Dafydd Gareth; Burn, John; Holinski-Feder, Elke; Bertario, Lucio; Bonanni, Bernardo; Lindblom, Annika; Levi, Zohar; Macrae, Finlay; Winship, Ingrid; Plazzer, John-Paul; Sijmons, Rolf; Laghi, Luigi; Valle Della, Adriana; Heinimann, Karl; Half, Elizabeth; Lopez-Koestner, Francisco; Alvarez-Valenzuela, Karin; Scott, Rodney J.; Katz, Lior; Laish, Ido; Vainer, Elez; Vaccaro, Carlos Alberto; Carraro, Dirce Maria; Gluck, Nathan; Abu-Freha, Naim; Stakelum, Aine; Kennelly, Rory; Winter, Des; Rossi, Benedito Mauro; Greenblatt, Marc; Bohorquez, Mabel; Sheth, Harsh; Tibiletti, Maria Grazia; Lino-Silva, Leonardo S.; Horisberger, Karoline; Portenkirchner, Carmen; Nascimento, Ivana; Rossi, Norma Teresa; da Silva, Leandro Apolinário; Thomas, Huw; Zaránd, Attila; Mecklin, Jukka-Pekka; Pylvänäinen, Kirsi; Renkonen-Sinisalo, Laura; Lepistö, Anna; Peltomäki, Päivi; Therkildsen, Christina; Lindberg, Lars Joachim; Thorlacius-Ussing, Ole; von Knebel, Doeberitz Magnus; Loeffler, Markus; Rahner, Nils; Steinke-Lange, Verena; Schmiegel, Wolff; Vangala, Deepak; Perne, Claudia; Hüneburg, Robert; de Vargas, Aída Falcón; Latchford, Andrew; Gerdes, Anne-Marie; Backman, Ann-Sofie; Guillén-Ponce, Carmen; Snyder, Carrie; Lautrup, Charlotte K.; Amor, David; Palmero, Edenir; Stoffel, Elena; Duijkers, Floor; Hall, Michael J.; Hampel, Heather; Williams, Heinric; Okkels, Henrik; Lubiński, Jan; Reece, Jeanette; Ngeow, Joanne; Guillem, Jose G.; Arnold, Julie; Wadt, Karin; Monahan, Kevin; Senter, Leigha; Rasmussen, Lene J.; van Hest, Liselotte P.; Ricciardiello, Luigi; Kohonen-Corish, Maija R. J.; Ligtenberg, Marjolijn J. L.; Southey, Melissa; Aronson, Melyssa; Zahary, Mohd N.; Samadder, N. Jewel; Poplawski, Nicola; Hoogerbrugge, Nicoline; Morrison, Patrick J.; James, Paul; Lee, Grant; Chen-Shtoyerman, Rakefet; Ankathil, Ravindran; Pai, Rish; Ward, Robyn; Parry, Susan; Dębniak, Tadeusz; John, Thomas; van Overeem, Hansen Thomas; Caldés, Trinidad; Yamaguchi, Tatsuro; Barca-Tierno, Verónica; Garre, Pilar; Cavestro, Giulia Martina; Weitz, Jürgen; Redler, Silke; Büttner, Reinhard; Heuveline, Vincent; Hopper, John L.; Win, Aung Ko; Lindor, Noralane; Gallinger, Steven; Le Marchand, Loïc; Newcomb, Polly A.; Figueiredo, Jane; Buchanan, Daniel D.; Thibodeau, Stephen N.; ten Broeke, Sanne W.; Hovig, Eivind; Nakken, Sigve; Pineda, Marta; Dueñas, Nuria; Brunet, Joan; Green, Kate; Lalloo, Fiona; Newton, Katie; Crosbie, Emma J.; Mints, Miriam; Tjandra, Douglas; Neffa, Florencia; Esperon, Patricia; Kariv, Revital; Rosner, Guy; Pavicic, Walter Hernán; Kalfayan, Pablo; Torrezan, Giovana Tardin; Bassaneze, Thiago; Martin, Claudia; Moslein, Gabriela; Ahadova, Aysel; Kloor, Matthias; Sampson, Julian R.; Jenkins, Mark A.; The European Hereditary Tumour Group (EHTG); the International Mismatch Repair Consortium (IMRC) (Biomed Central, 2022)Objective: To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all ...
Clinical characteristics of pancreatic and biliary tract cancers in Lynch syndrome : A retrospective analysis from the Finnish National Lynch Syndrome Research Registry Zalevskaja, Kristina; Mecklin, Jukka-Pekka; Seppälä, Toni T. (Frontiers Media SA, 2023)Introduction: Patients with Lynch syndrome (LS) have an increased lifetime risk of pancreatic cancer (PC) and biliary tract cancer (BTC). These cancers have a notoriously pessimistic prognosis due to late diagnosis and ...