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

Variants in mismatch repair genes (MLH1, MSH2, MSH6), with gastric and duodenal cancer incidence varying by gene

Lynch syndrome is associated with gastric and duodenal cancer, but risk estimates and the role of upper endoscopy surveillance remain uncertain. This systematic review and meta-analysis (PubMed, Embase, Scopus, through January 2026) analysed 35 studies including 33,530 patients with genetically confirmed Lynch syndrome. The pooled incidence rate is 0.98 per 1,000 person-years (95% CI 0.54-1.42) for gastric cancer and 1.93 (0.71-3.15) for duodenal cancer; gastric cancer rates were 0.44 for MLH1, 1.27 for MSH2 and 0.03 for MSH6, and duodenal cancer rates 0.95 for MLH1 and 0.46 for MSH2. In exploratory comparative analyses based on two observational studies per outcome, oesophagogastroduodenoscopy surveillance was associated with a lower observed gastric cancer risk (RR 0.31; 95% CI 0.14-0.69) but not with a different duodenal cancer risk (RR 0.78; 0.35-1.74). The authors stress that comparative evidence is limited and observational and that these findings establish neither reduced cancer incidence nor a survival benefit, while supporting further evaluation of risk-adapted upper endoscopic surveillance.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The most useful finding in practice is the variation by gene: 1.27 for MSH2 versus 0.03 for MSH6 per 1,000 person-years for gastric cancer, a gap that argues for gene-adapted rather than uniform surveillance, even though the abstract gives no confidence interval for these gene-level rates. The RR of 0.31 in favour of surveillance rests on only two observational studies, exposed to the biases inherent in this type of comparison, and the authors themselves present it only as exploratory: I would not change practice on this basis. The review does, however, justify a prospective evaluation of upper endoscopy adapted to risk, that is to the gene, rather than its extension to all carriers.

Analysis by Dr Thibaut Benquey