Cancer risks in lynch syndrome carriers: a systematic review and meta-analysis
A partir d'une revue systématique de la littérature publiée jusqu'en décembre 2024 (33 études), cette méta-analyse évalue, par type de mutation et par âge, le risque de développer un cancer (côlon-rectum, endomètre, ovaire...) chez des patients atteints d'un syndrome de Lynch
Background : Lynch Syndrome (LS), caused by pathogenic variants (PVs) in mismatch repair (MMR) genes, increases the risk of several cancers. Surveillance guidelines vary internationally due to inconsistent risk estimates. This study refines cancer risk estimates by gene, sex, and age to support personalized recommendations.
Methods : This meta-analysis included studies reporting cumulative cancer risks in genetically confirmed LS PV carriers. PubMed was searched until December 31, 2024. Following the MOOSE guideline, data were extracted independently by two reviewers and analyzed using fixed (n = 2 estimates) or random-effects models (n > 2 estimates), stratified by gene, sex, cancer site, and study design
LS retrospective family studies (LSRF), LS prospective cohort (LSPC), and population-based case-control (PBCC).
Results : Thirty-three studies were included, mostly LSRF. Meta-analysis of LSRF showed that colorectal cancer risk by age 40 was markedly lower in MSH6 and PMS2 carriers (<2%) than in MLH1 and MSH2 (>4%). For endometrial cancer, risks at 50 y were 8.3%[5.1–13.4], 8.7%[3.8–18.7], 5.2%[2.3–11.2] and 3.0%[1.0–8.0] for MLH1, MSH2, MSH6 and PMS2 respectively. For ovarian cancer, risks at 40 y were 1.2%[0.6–2.7] and 0.9%[0.5–1.8] for MLH1 and MSH2, respectively. Few studies addressed other cancer types, highlighting the need for additional data.
Conclusions : This is the first meta-analysis providing stratified cancer risk estimates by cancer site, gene, and study design. These findings support gene-specific surveillance strategies, such as initiating colonoscopy at age 30–35 for MSH6 and PMS2 carriers, postponing hysterectomy after 50 y for PMS2 carriers, and delaying oophorectomy after 45 y for MLH1 and MSH2 PV carriers.
Journal of the National Cancer Institute , résumé, 2025