Familial gastric cancers with Li-Fraumeni Syndrome: A case repast

TO THE EDITORAlthough the incidence of gastric cancer has declined somewhat in recent years, it remains one of the most common cancers worldwide[1], and is the most common cancer in East Asian countries such as Korea and Japan[2].In terms of the genetics of gastric cancer, mutations in CDH1 (E-cadberin) have been associated with hereditary diffuse gastric cancer (HDGC). The first germline mutation in CDH1 was reported in a large Maori HDGC family[1],with subsequent corroborations in Western and Asian HDGC families[3-5], CDH1 mutations are believed to be associated with up to 50% of HDGC families[5], but have not been linked with sporadic or intestinal types of gastric cancer[5].

Family history of cancer in Chinese gastric cancer patients

Objective:The aim of the study was to investigate the influence of gastric cancer family history in the gastric cancer (GC) patients. Methods: Gastric cancer family histories within second degree relatives and clinicopathological features were obtained for 497 patients. Results:Of the 497 probands,235 probands were incorporated into familial gastric cancer (FGC) group (there were at least two GC members in the family); 262 probands were included in the non-FGC group (relatives only affected with non-GCs). Of 614 tumors in relatives,GC was the most frequent,followed by lung cancer,esophageal cancer,hepatocellular cancer,colorectal cancer,urogenital cancer,breast cancer,and pancreatic cancer. Most affected members aggregated within first-degree relatives. The ratio of males to females in affected first-degree relatives was usually higher in male probands. Paternal history of GC was a strong risk for GC in males,while risk of GC by maternal history of GCs was increased in females. Difference in tumor histological types between the two groups was derived from an excess of diffuse GC in non-FGC male probands. The lower site was the most frequent tumor location in all subgroups. Conclusion:Distribution of associated non-GCs in a family history of GC may vary with geographic areas. GC may have different genetic and/or environmental etiology in different families,and a certain subtype may be inherited in a male-influenced fashion.

A multicenter study assessing the prevalence of germline genetic alterations in Chinese gastric-cancer patients

Background Approximately 10%of patients with gastric cancer(GC)have a genetic predisposition toward the disease.However,there is scant knowledge regarding germline mutations in predisposing genes in the Chinese GC population.This study aimed to determine the spectrum and distribution of predisposing gene mutations among Chinese GC patients known to have hereditary high-risk factors for cancer.Methods A total of 40 GC patients from 40 families were recruited from seven medical institutions in China.Next-generation sequencing was performed on 171 genes associated with cancer predisposition.For probands carrying pathogenic/likely pathogenic germline variants,Sanger sequencing was applied to validate the variants in the probands as well as their relatives.Results According to sequencing results,25.0%(10/40)of the patients carried a combined total of 10 pathogenic or likely pathogenic germline variants involving nine different genes:CDH1(n=1),MLH1(n=1),MSH2(n=1),CHEK2(n=1),BLM(n=1),EXT2(n=1),PALB2(n=1),ERCC2(n=1),and SPINK1(n=2).In addition,129 variants of uncertain significance were identified in 27 patients.Conclusions This study indicates that approximately one in every four Chinese GC patients with hereditary high risk factors may harbor pathogenic/likely pathogenic germline alterations in cancer-susceptibility genes.The results further indicate a unique genetic background for GC among Chinese patients.