Incidence of colorectal neoplasia among young patients with Lynch syndrome. Results of the PRED-IdF cohort

Guillaume PERROD1, Elise Coffin1, Celine Lekhal2, Géraldine PERKINS1, Marion DHOOGE3, Stanislass Chaussade3, Enrique Perez Cuadrado Robles1, Jeanne Netter-Coti4, Yann PARC4, Jérome BELLANGER4, Olivier CARON5, David MALKA5, Chrystelle Colas6, Bruno BUECHER6, Emmanuelle Fourme6, Veronica CUSIN7, Robert BENAMOUZIG2, Pierre Laurent-Puig1, Christophe CELLIER1

1Hôpital Européen Georges Pompidou, Paris, France. 2Hôpital Avicenne, Paris, France. 3Hôpital Cochin, Paris, France. 4Hôpital Saint-Antoine, Paris, France. 5Institut Gustave Roussi, Paris, France. 6Institut Curie, Paris, France. 7Groupe Hospitalier la Pitié Salpêtrière, Paris, France



Patients with Lynch syndrome are exposed to colorectal cancer (CRC) development, even at a young age. International guidelines recommend colorectal screening, starting from the age of 20-25 years-old, every 1 to 2 years. It is not known whether colorectal screening could be adapted according to mutation type.



From January 2010 to January 2018, all patients under 50 years-old and followed within the PRED-IdF network with a proven germline mutation were consecutively  included. Demographics, type of mutation and colonoscopies data were collected. We defined the composite criteria “colorectal neoplasia” (CN) as the detection of any of the following event: CRC, adenoma and/or sessile serrated lesion (SSL).



A total of 708 patients were included (Median age 33.6±8.4 years, male ratio 0.7 and mutations: MLH1 33.5%, MSH2 45.6%, MSH6 15.3%, PMS2 4.2% and EPCAM 1.4%) with a median follow-up of 55 [0-340] months. The incidence of CN, CRC, Adenoma and SSL were respectively of 53%, 22.9%, 37.9% and 6.6%. Among patients with MSH6 mutation, the age at first event was older than for other mutations, p=0.038 (figure 1). After univariate and multivariate analysis, age (HR : 1,038 IC95[1.026-1.116]), male sex (HR : 1.460 IC95[1.017-1.061]), and tobacco use (HR : 1.672 IC95[1.252-2.233]), were associated with a higher risk of CN occurrence.



MSH6 and other demographic factors may be associated with an older age for CN occurrence. In order to delay the age of screening colonoscopies, a specific algorithm risk must be developed and evaluated in dedicated studies.