Case series of three patients with hereditary diffuse gastric cancer in a single family: Three case reports and review of literature

Abstract

BACKGROUND Hereditary diffuse gastric cancer (HDGC) is a familial cancer syndrome often associated with germline mutations in the CDH1 gene. However, the frequency of CDH1 mutations is low in patients with HDGC in East Asian countries. Herein, we report three cases of HDGC harboring a missense CDH1 variant, c.1679C>G, from a single Japanese family. CASE SUMMARY A 26-year-old female (Case 1) and a 51-year-old male (father of Case 1), who had a strong family history of gastric cancer, were diagnosed with advanced diffuse gastric cancer. After genetic counselling, a 25-year-old younger brother of Case 1 underwent surveillance esophagogastroduodenoscopy that detected small signet ring cell carcinoma foci as multiple pale lesions in the gastric mucosa. Genetic analysis revealed a CDH1 c.1679C>G variant in all three patients. CONCLUSION It is important for individuals suspected of having HDGC to be actively offered genetics evaluation. This report will contribute to an increased awareness of HDGC.

Hereditary Diffuse Gastric Cancer in a Japanese Family with CDH1 Mutation: Three Individuals Undergoing Total Gastrectomy Following Presymptomatic Genomic Diagnosis

“…In general, the onset of the disease occurs at a young age (8-13). In other Japanese families with CDH1 mutation, most cases reported were in their 20s or 30s (5)(6)(7)(8)(9)(10)(11)(12)(13). The age distribution in the present family may have been related to other factors contributing to the development of gastric cancer.…”

“…Despite the high incidences of gastric cancers in East Asian countries compared with Western countries, HDGC harboring CDH 1 variants has rarely been reported. Although several Japanese HDGC families with CDH 1 variant have been reported to date [8][9][10][11][12][13], awareness of this clinical entity remains low.…”

Hereditary diffuse gastric cancer in a Japanese family with CDH1 mutation three case reports

“…This variant was previously described by Benusiglio et al [ 16 ] and registered as pathogenic in the available archive ClinVar ( https://www.ncbi.nlm.nih.gov/clinvar/ ). Of note, although several Japanese families with CDH1 -related HDGC have been reported [ 9 – 14 ], to our knowledge, this variant type was not identified and this is the largest number of family members with HDGC reported to date in Japan.…”

“…In general, the onset of the disease occurs at a young age. In other families with CDH1 mutation including Japanese, most cases reported were in their 20 s or 30 s [ 4 – 14 ]. The age distribution in the present family may have been related to other factors contributing to the development of gastric cancer.…”

“…Despite the high incidences of gastric cancers in East Asian countries compared with Western countries, HDGC harboring CDH1 variants has rarely been reported. Although several Japanese HDGC families with CDH1 variant have been reported to date [9][10][11][12][13][14], awareness of this clinical entity remains low.…”