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



Seppala, Toni, Pylvanainen, Kirsi, Evans, Dafydd Gareth, Jarvinen, Heikki, Renkonen-Sinisalo, Laura, Bernstein, Inge, Holinski-Feder, Elke, Sala, Paola, Lindblom, Annika, Macrae, Finlay
et al (show 29 more authors) (2017) Colorectal cancer incidence in <i>path_MLH1</i> carriers subjected to different follow-up protocols: a Prospective Lynch Syndrome Database report. HEREDITARY CANCER IN CLINICAL PRACTICE, 15 (1). 18-.

Access the full-text of this item by clicking on the Open Access link.
[img] Text
Colorectal cancer incidence in path_MLH1 carriers subjected to different follow-up protocols: a Prospective Lynch Syndrome Database report.pdf - Published version

Download (621kB) | Preview

Abstract

<h4>Background</h4>We have previously reported a high incidence of colorectal cancer (CRC) in carriers of pathogenic <i>MLH1</i> variants <i>(path_MLH1</i>) despite follow-up with colonoscopy including polypectomy.<h4>Methods</h4>The cohort included Finnish carriers enrolled in 3-yearly colonoscopy (<i>n</i> = 505; 4625 observation years) and carriers from other countries enrolled in colonoscopy 2-yearly or more frequently (<i>n</i> = 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.<h4>Results</h4>Cumulative CRC incidences in carriers of <i>path_MLH1</i> 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 (<i>p</i> > 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).<h4>Conclusions</h4>The hypothesis that the high incidence of CRC in <i>path_MLH1</i> 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 <i>path_MLH1</i> 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.

Item Type: Article
Uncontrolled Keywords: Lynch syndrome, Hereditary non-polyposis colorectal cancer, Colorectal cancer, Microsatellite instability
Depositing User: Symplectic Admin
Date Deposited: 02 Oct 2019 09:44
Last Modified: 12 Oct 2023 13:50
DOI: 10.1186/s13053-017-0078-5
Open Access URL: https://doi.org/10.1186/s13053-017-0078-5
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3056680