CDH1 mutations in gastric cancers are not associated with family history

CDH1 mutation is the most frequent genetic alteration in hereditary diffuse gastric cancer (GC) and early onset diffuse GC patients. However, the incidence of CDH1 mutations in sporadic GC with or without family history has not been studied. This retrospective study includes a total of 993 Korean patients with primary advanced GC who underwent surgery and received palliative chemotherapy. Targeted deep sequencing was performed in all cases and family history of GC was searched with survival analysis. We found CDH1 alterations in 146 of 993 patients (14.7 %) and 8 were germline (0.8 %). Out of 146 patients with CDH1 mutations, 25 (17.1 %) had a family history of GC in one of their first relatives, and 12 patients (8.2 %) were diagnosed with familial GC (FGC). All cases with FGC were diffuse type by Lauren classification, and only one harbored a previously reported germline mutation of CDH1 (c.2638 G > A) and the remaining 11 harbored known somatic CDH1 mutations. Among all patients with CDH1 mutation, there was no significant survival difference between patients with family history or FGC. In the 847 patients without CDH1 mutation, 189 (22.3 %) had a family history of GC and 92 patients (10.9 %) were FGC. CDH1 mutations were more frequent in patients with early onset (<45 years) GC (45.5 %) compared with patients with late onset GC (10.9 %) (p = 0.001), but were not significantly associated with the family history of GC (p > 0.05). CDH1 mutations are mostly somatic and typically are not associated with family history.