Colorectal cancer incidence in path_MLH1 carriers subjected to different follow-up protocols : a Prospective Lynch Syndrome Database report

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Seppala , T , Pylvanainen , K , Evans , D G , Jarvinen , H , Renkonen-Sinisalo , L , Bernstein , I , Holinski-Feder , E , Sala , P , Lindblom , A , Macrae , F , Blanco , I , Sijmons , R , Jeffries , J , Vasen , H , Burn , J , Nakken , S , Hovig , E , Rodland , E A , Tharmaratnam , K , Cappel , W H D V T N , Hill , J , Wijnen , J , Jenkins , M , Genuardi , M , Green , K , Lalloo , F , Sunde , L , Mints , M , Bertario , L , Pineda , M , Navarro , M , Morak , M , Frayling , I M , Plazzer , J-P , Sampson , J R , Capella , G , Moslein , G , Mecklin , J-P , Moller , P & Collaboration Mallorca Grp 2017 , ' Colorectal cancer incidence in path_MLH1 carriers subjected to different follow-up protocols : a Prospective Lynch Syndrome Database report ' , Hereditary Cancer in Clinical Practice , vol. 15 , 18 .

Title: Colorectal cancer incidence in path_MLH1 carriers subjected to different follow-up protocols : a Prospective Lynch Syndrome Database report
Author: Seppala, Toni; Pylvanainen, Kirsi; Evans, Dafydd Gareth; Jarvinen, Heikki; Renkonen-Sinisalo, Laura; Bernstein, Inge; Holinski-Feder, Elke; Sala, Paola; Lindblom, Annika; Macrae, Finlay; Blanco, Ignacio; Sijmons, Rolf; Jeffries, Jacqueline; Vasen, Hans; Burn, John; Nakken, Sigve; Hovig, Eivind; Rodland, Einar Andreas; Tharmaratnam, Kukatharmini; Cappel, Wouter H. de Vos tot Nederveen; Hill, James; Wijnen, Juul; Jenkins, Mark; Genuardi, Maurizio; Green, Kate; Lalloo, Fiona; Sunde, Lone; Mints, Miriam; Bertario, Lucio; Pineda, Marta; Navarro, Matilde; Morak, Monika; Frayling, Ian M.; Plazzer, John-Paul; Sampson, Julian R.; Capella, Gabriel; Moslein, Gabriela; Mecklin, Jukka-Pekka; Moller, Pal; Collaboration Mallorca Grp
Contributor organization: Clinicum
Department of Surgery
University of Helsinki
Heikki Järvinen / Principal Investigator
II kirurgian klinikka
Genome-Scale Biology (GSB) Research Program
Research Programs Unit
HUS Abdominal Center
Date: 2017-10-10
Language: eng
Number of pages: 10
Belongs to series: Hereditary Cancer in Clinical Practice
ISSN: 1731-2302
Abstract: Background: We have previously reported a high incidence of colorectal cancer (CRC) in carriers of pathogenic MLH1 variants (path_MLH1) despite follow-up with colonoscopy including polypectomy. Methods: The cohort included Finnish carriers enrolled in 3-yearly colonoscopy (n = 505; 4625 observation years) and carriers from other countries enrolled in colonoscopy 2-yearly or more frequently (n = 439; 3299 observation years). We examined whether the longer interval between colonoscopies in Finland could explain the high incidence of CRC and whether disease expression correlated with differences in population CRC incidence. Results: Cumulative CRC incidences in carriers of path_MLH1 at 70-years of age were 41% for males and 36% for females in the Finnish series and 58% and 55% in the non-Finnish series, respectively (p > 0.05). Mean time from last colonoscopy to CRC was 32.7 months in the Finnish compared to 31.0 months in the non-Finnish (p > 0.05) and was therefore unaffected by the recommended colonoscopy interval. Differences in population incidence of CRC could not explain the lower point estimates for CRC in the Finnish series. Ten-year overall survival after CRC was similar for the Finnish and non-Finnish series (88% and 91%, respectively; p > 0.05). Conclusions: The hypothesis that the high incidence of CRC in path_MLH1 carriers was caused by a higher incidence in the Finnish series was not valid. We discuss whether the results were influenced by methodological shortcomings in our study or whether the assumption that a shorter interval between colonoscopies leads to a lower CRC incidence may be wrong. This second possibility is intriguing, because it suggests the dogma that CRC in path_MLH1 carriers develops from polyps that can be detected at colonoscopy and removed to prevent CRC may be erroneous. In view of the excellent 10-year overall survival in the Finnish and non-Finnish series we remain strong advocates of current surveillance practices for those with LS pending studies that will inform new recommendations on the best surveillance interval.
Subject: Lynch syndrome
Hereditary non-polyposis colorectal cancer
Colorectal cancer
Microsatellite instability
3122 Cancers
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion
Funder: Helsingin yliopisto
Grant number:

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