Risk of Gastric and Small Intestinal Cancer in Patients With Lynch syndrome - Data From a Large, Community-Based U.S. Population.

ABSTRACT

INTRODUCTION: Risk of gastric and small intestinal cancer in Lynch syndrome (LS) remains poorly understood. We investigated the risk of gastric and small intestinal cancer in patients with LS in a large, community-based population. METHODS: This retrospective cohort study included all patients diagnosed with LS between 1/1/1997-12/31/2020 at Kaiser Permanente Northern California. Cumulative incidence of gastric cancer and small intestinal cancer was calculated using competing risk methodology. RESULTS: Among 1106 LS patients with a median follow-up of 19.3 years (interquartile range [IQR] 9.4-24.0 years), 11 developed gastric cancer (8 MSH2, 2 MLH1 and 1 PMS2) with the median diagnosis age of 56 years (IQR 42-63 years); 11 developed small intestinal cancer (6 MSH2, 3 MLH1, 1 MSH6 and 1 PMS2) with the median diagnosis age of 57 years (IQR 50-66 years). Cumulative incidence by age 80 years was 7.26% (95% confidence internal [CI], 1.80-18.03%) for men and 3.43% (95% CI, 0.50-11.71%) for women for gastric cancer, and was 7.28% (95% CI, 3.19-13.63%) for men and 2.21% (95% CI, 0.23-9.19%) for women for small intestinal cancer. Pathogenic variants (PV) carriers of MSH2 and MLH1 had the highest risk of gastric and small intestinal cancer. History of Helicobacter pylori (H. pylori) infection was associated with increased risk of gastric cancer (adjusted odds ratio 5.52; 95% CI, 1.72-17.75). DISCUSSION: Patients with LS, particularly MSH2 and MLH1 PV carriers, had significantly increased lifetime risk of gastric and small intestinal cancer. Testing and treatment of H. pylori should be considered for all patients with LS.