Impact of surveillance colonoscopy on colorectal cancer incidence and mortality in Lynch syndrome: a national observational cohort study of patients in the English NHS 2010–2022
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background Lynch syndrome (LS) is a cancer susceptibility syndrome caused by germline pathogenic variants in DNA mismatch repair (MMR) genes. Due to increased risk of colorectal cancer (CRC), enhanced colonoscopic surveillance is recommended for heterozygote MMR carriers.
Objective Using a registry of English patients with LS linked to digital National Health Service records, we aimed to assess adherence of MMR carriers to national surveillance guidelines and to determine the impact of surveillance on CRC incidence and mortality.
Design We described the frequency of colonoscopies in 4732 MMR carriers and used logistic regression to determine predictors of surveillance adherence. For MMR carriers with a record of surveillance and those without, we estimated age-specific annual CRC incidence rates (AS-AIRs) and cumulative lifetime risks; assessed for stage shift by comparing CRC stage distributions and stage-specific AS-AIRs; and estimated risks of death from CRC and any cause using Kaplan-Meier methods and Cox proportional hazards regression.
Results Surveillance at a mean interval of ≤3 years (n=3028) was associated with a decrease in CRC-specific and all-cause mortality, without an associated change in total CRC incidence, even after multivariate adjustment. No strong evidence of stage shift was observed. Colonoscopic surveillance at a mean interval of ≤2 years (n=1569) was associated with an increase in total CRC incidence. Incidence of early-stage cancers was also higher, with no corresponding decrease in late-stage cancers, which may reflect the short follow-up period, spectrum bias, or the impact of overdiagnosis.
Conclusion The observed reduction in all-cause mortality among regularly surveilled MMR carriers may indicate an impact of surveillance on CRC-specific mortality, though in the context of a non-randomised study could also reflect the influence of selection bias.
Objective Using a registry of English patients with LS linked to digital National Health Service records, we aimed to assess adherence of MMR carriers to national surveillance guidelines and to determine the impact of surveillance on CRC incidence and mortality.
Design We described the frequency of colonoscopies in 4732 MMR carriers and used logistic regression to determine predictors of surveillance adherence. For MMR carriers with a record of surveillance and those without, we estimated age-specific annual CRC incidence rates (AS-AIRs) and cumulative lifetime risks; assessed for stage shift by comparing CRC stage distributions and stage-specific AS-AIRs; and estimated risks of death from CRC and any cause using Kaplan-Meier methods and Cox proportional hazards regression.
Results Surveillance at a mean interval of ≤3 years (n=3028) was associated with a decrease in CRC-specific and all-cause mortality, without an associated change in total CRC incidence, even after multivariate adjustment. No strong evidence of stage shift was observed. Colonoscopic surveillance at a mean interval of ≤2 years (n=1569) was associated with an increase in total CRC incidence. Incidence of early-stage cancers was also higher, with no corresponding decrease in late-stage cancers, which may reflect the short follow-up period, spectrum bias, or the impact of overdiagnosis.
Conclusion The observed reduction in all-cause mortality among regularly surveilled MMR carriers may indicate an impact of surveillance on CRC-specific mortality, though in the context of a non-randomised study could also reflect the influence of selection bias.
Date Issued
2026-08-06
Date Acceptance
2026-07-25
Citation
Gut, 2026
ISSN
0017-5749
Publisher
BMJ
Start Page
gutjnl-2025-337379
Journal / Book Title
Gut
Copyright Statement
© Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY. Published by BMJ Group.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/42562418
PII: gutjnl-2025-337379
Subjects
CANCER
CANCER GENETICS
COLONOSCOPY
SCREENING
SURVEILLANCE
Publication Status
Published online
Coverage Spatial
England
Date Publish Online
2026-08-06