Aims International guidelines recommend colorectal cancer (CRC) screening in patients
with Lynch Syndrome, starting from 20-25 years-old except for MSH6 and PMS2 where
the screening should start at 35 years-old.
Methods This is an observational analytical study. All consecutive patients under 50 years-old
followed within the PRED-IdF network with a proven germline mutation were included
between 2010 and 2019. Demographics, type of mutation and endoscopic data were collected.
To assess the age of primary colorectal event, we defined “colorectal neoplasia” (CN)
as the detection of any of the following events: CRC, adenoma and/or sessile serrated
lesion (SSL). Factors associated to CN were assessed by Cox regression survival analysis.
Results Seven hundred and eight patients (median age: 35 [15-50] years, male ratio 0.7) underwent
2429 colonoscopies during a median follow-up of 55 [0-350] months. They presented
with the following mutations: MLH1 (33.5%), MSH2 (45.6%), MSH6 (15.3%), PMS2 (4.2%)
and EPCAM (1.4%).
The quality of colonoscopy preparation was good in 73.5% of cases. Chromo-endoscopy
by indigo carmin was performed in 72.7% of cases.
The global incidence of CN, CRC, adenoma and SSL were respectively of 53%, 22.9%,
37.9% and 6.6%. For patients with MSH6 mutation, the age at first CN was significantly
older than for other mutations (p=0.038). Among these, we reported that 25% of CN
occurred before 35 years-old, including 7 adenomas including,1 advanced adenoma, 1
serrated adenoma and 5 CRC.
Overall, by multivariable analysis, age (HR: 1,038, CI95%: 1.026-1.116), male sex
(HR: 1.460, CI95% [1.017-1.061]), and tobacco use (HR: 1.672 CI95%: 1.252-2.233),
were associated with a higher incidence of CN.
Conclusions In this PRED-IdF study, MSH6 mutation and demographic factors were associated with
a delayed CN development. However, we report CN in MSH6 carriers before the age of
35 years, which may limit the application of recent guidelines.
