<i>CDH1</i> germline mutations in healthy individuals from families with the hereditary diffuse gastric cancer syndrome.

Abstract

The objective of this study was to determining the frequency of different sub-types of pathogenic <i>CDH1</i> 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 <i>CDH1</i> germline mutations. The collected variants were classified according to their subtype into the following classes: missense, non-sense, splicing, insertions and deletions. The χ² test was used to estimate if the difference observed between patients with gastric cancer (GC) and unaffected individuals was statistically significant. <i>CDH1</i> genetic screening data were retrieved for 224 patients with GC and 289 healthy individuals. Among the subjects that had tested <i>CDH1</i> 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, <i>CDH1</i> 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 <i>CDH1</i> germline mutations confer the same risk of developing GC.