Pathogenic variants (disease-causing) in the CTNNA1 gene are associated with Hereditary Diffuse Gastric Cancer (HDGC) syndrome, similar to CDH1. Individuals with pathogenic variants in CTNNA1 have an increased lifetime risk of diffuse gastric cancer, though the exact risk estimates are less well defined compared to CDH1. Some studies also suggest a possible association with lobular breast cancer, but the evidence is still emerging. Management of CTNNA1–related tumor risk includes regular surveillance tailored to guidelines to detect tumors early as well as risk-reducing surgeries. CTNNA1 variants are not known to be more common in the Ashkenazi Jewish population.
Pathogenic variants in CTNNA1 exhibit autosomal dominant inheritance. This means there is a 50% chance the condition can be passed from generation-to-generation. First degree relatives (parents, siblings, children) have a 50% chance to have the same pathogenic variant whereas second degree relatives (grandparents, aunts/uncles, nieces/nephews, half-siblings) have a 25% chance. More distant relatives have lower chances of having the same pathogenic variant when one is identified in the family.
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Written December 2025
