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

作者：Catherine Huntley, Lucy Loong, Corinne Mallinson, Tameera Rahman, Bethany Torr, Sophie Allen, Isaac Allen, Hend Hassan, Yvonne Wallburga Joko Fru, Daniela Tataru, Lizz Paley, Sally Vernon, Richard S. Houlston, David C. Muller, Fiona Lalloo, Adam Shaw, John Burn, Eva Morris, Marc Tischkowitz, Antonis C. Antoniou, Paul D.P. Pharoah, Kevin Monahan, Steven Hardy, Clare Turnbull · 发表于：Gut · 年份：2026 · DOI：10.1136/gutjnl-2025-337379 · 研究领域：Genetic factors in colorectal cancer

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 LS patients 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 4,732 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...