Gastric and Duodenal Cancer in Lynch Syndrome: Incidence and Endoscopic Surveillance-Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Lynch syndrome (LS) is associated with gastric cancer (GC) and duodenal cancer (DC), but risk estimates and the role of upper endoscopy surveillance remain uncertain.

METHODS

We searched PubMed, Embase, and Scopus through January 2026. Cohort studies and clinical trials reporting GC or DC incidence in genetically confirmed LS, or comparing patients with and without esophagogastroduodenoscopy (EGD) surveillance, were included. Incidence rates per 1,000 person-years (p-y) were pooled overall and by mismatch repair (MMR) gene. When available, risk ratios compared EGD surveillance versus no surveillance.

RESULTS

Thirty-five studies including 33,530 patients with LS were analyzed. The pooled incidence rate per 1,000 p-y was 0.98 (95% CI, 0.54-1.42) for GC and 1.93 (95% CI, 0.71-3.15) for DC. GC incidence rates were 0.44 for MLH1, 1.27 for MSH2, and 0.03 for MSH6. DC incidence rates were 0.95 for MLH1 and 0.46 for MSH2. In exploratory comparative analyses based on two observational studies per outcome, EGD surveillance was associated with lower observed GC risk (RR, 0.31; 95% CI, 0.14-0.69), but not with different observed DC risk (RR, 0.78; 95% CI, 0.35-1.74).

CONCLUSIONS

LS is associated with clinically relevant GC and DC incidence, with risk varying by MMR gene. Current comparative evidence for EGD surveillance is limited and observational. These findings support further evaluation of risk-adapted upper endoscopic surveillance, but do not establish reduced cancer incidence or survival benefit.