Dental agenesis as a novel phenotypical feature associated with hereditary diffuse gastric cancer in China.

Background: Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant gastric cancer associated with germline CDH1 mutations. Carriers of CDH1 mutations have a higher risk of developing gastric cancer at a younger age, highlighting the need for a phenotypic feature for early diagnosis and management.

Methods: We analysed 121 patients with gastric cancer who underwent genetic testing at the National Cancer Center in China. CDH1 mutation status was assessed using next-generation sequencing. Fisher's exact test and Mann-Whitney U test were performed to compare clinicopathological features between CDH1-mutated and non-mutated patient groups.

Results: Among 121 index cases, three CDH1 germline mutation carriers (2.5%) were identified. Mutation carriers were diagnosed at a significantly younger age compared with non-carriers (p<0.05). Notably, two patients in our cohort exhibited congenital tooth agenesis, a phenotypical feature rarely reported in patients with HDGC and previously undocumented in East Asian cohorts.

Conclusion: Congenital tooth agenesis represents a phenotypic manifestation associated with CDH1 germline mutations. Awareness of such features could enhance recognition of high-risk individuals and support genetic counselling and surveillance strategies. Further studies are needed to confirm these associations.