Risk of Gastric Cancer and Utility of Endoscopic Screening for Lynch Syndrome Patients

Background: Lynch syndrome (LS) is an autosomal dominant hereditary condition associated with a genetic predisposition to several cancers. Prior studies have shown an increased risk of gastric cancer (GC) in LS patients. The aim of this study was to synthesize the evidence for gastric cancer risk across Lynch syndrome-associated mutations and to assess the diagnostic utility of endoscopic screening for gastric cancer in these patients. Methods: A systematic literature review and meta-analysis of LS-associated gastric cancer risk and the diagnostic utility of endoscopic gastric cancer screening was conducted in accordance with PRISMA guidelines and GRADE methodology. Results: The results of this study found an elevated risk of GC in LS patients. Cumulative lifetime risk of GC in LS patients ranged from 2.6% to 38.7% when assessing across all LS mutations. Cumulative incidence ranged from 2.0% to 41.0%. When assessing cumulative incidence across specific LS mutations, MSH2 mutation carriers showed the highest cumulative incidence. RR across specific mutation carriers was generally highest in MSH2 carriers. A meta-analysis of 5 studies reporting diagnostic utility of endoscopic screening for gastric cancer in LS patients revealed a 2% incidence of GC (95% CI, 1.4%−2.9%). Conclusions: Gastric cancer risk in LS patients is greater than in the general population. Endoscopic screening yields low rates of GC in LS patients. Higher quality studies including RCTs are required to more accurately define GC risk and the yield of endoscopic surveillance in LS patients.