Multicenter retrospective cohort study of association of germline CDH1 variants and lifetime cancer risk

Approximately 1% to 3% of gastric cancers and 5% of lobular breast cancers are hereditary. Loss of function CDH1 gene variants are the most common gene variants associated with these cancers. Previously, in individuals with these variants the lifetime risk of gastric cancer was estimated to be approximately 25% to 83%, whereas the risk of breast cancer was estimated to be approximately 39% to 55%. In a multicenter, retrospective cohort and modeling study that included 213 families with at least 1 family member with a CDH1 pathogenic or likely pathogenic variant, the cumulative risk of gastric cancer by age 80 years was 7% to 10%, which was lower than previously described, whereas the lifetime risk of breast cancer among female carriers was 36.8%, which was similar to prior estimates. The authors conclude that these finding may inform current management of individuals with germline CDH1 variants.