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

Abstract

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant gastric cancer associated with germline <i>CDH1</i> mutations. Carriers of <i>CDH1</i> 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. We analysed 121 patients with gastric cancer who underwent genetic testing at the National Cancer Center in China. <i>CDH1</i> mutation status was assessed using next-generation sequencing. Fisher's exact test and Mann-Whitney U test were performed to compare clinicopathological features between <i>CDH1</i>-mutated and non-mutated patient groups. Among 121 index cases, three <i>CDH1</i> germline mutation carriers (2.5%) were identified. Mutation carriers were diagnosed at a significantly younger age compared with non-carriers (<i>p</i><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. Congenital tooth agenesis represents a phenotypic manifestation associated with <i>CDH1</i> 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.