New Estimates of Cancer Risk with Germline CDH1 Variants

Germline pathogenic (P) or likely pathogenic (LP) loss-of-function variants in the CDH1 gene are known to increase lifetime risks of gastric cancer and breast cancer, but the risk estimates to date (~50%) have been based on select populations, usually without consideration of the influence of cancer in other family members.

To better estimate these risks, researchers conducted a retrospective cohort study in North America involving 7323 individuals from 213 families that had more than one family member with a P/LP CDH1 variant. Genotyping was performed by certified diagnostic laboratories, with single-site analysis if a CDH1 variant existed in the family, single CDH1 gene analysis if personal and family history suggested hereditary diffuse g…