germline mutations in healthy individuals from families with the hereditary diffuse gastric cancer syndrome.

The objective of this study was to determining the frequency of different sub-types of pathogenic germline mutations in healthy and asymptomatic individuals from families with the hereditary diffuse gastric cancer (HDGC) syndrome. Relevant literature dating from 1998 to 2019 was systematically searched for data on germline mutations. The collected variants were classified according to their subtype into the following classes: missense, non-sense, splicing, insertions and deletions. The χ test was used to estimate if the difference observed between patients with gastric cancer (GC) and unaffected individuals was statistically significant. genetic screening data were retrieved for 224 patients with GC and 289 healthy individuals. Among the subjects that had tested positive, splicing mutations were found in 30.4% of the healthy individuals and in 15.2% of the patients with GC (p=0.0076). Missense mutations were also found to occur in healthy subjects with higher frequency (22.2%) than in GC-affected individuals (18.3%), but the difference was not significant in this case. In families meeting the clinical criteria for the HDGC syndrome, splicing and missense germline mutations have been reported to occur with higher frequency in healthy subjects than in patients with cancer. This preliminary observation suggests that not all pathogenic germline mutations confer the same risk of developing GC.