Germline CDH1 variants in hereditary diffuse gastric cancer syndrome with focus on younger women

Purpose The objective of this study was to determine the male and female frequency of diffuse gastric cancer (DGC), the age at diagnosis, and the country of origin in a selected population with germline CDH1 variants from families with the hereditary diffuse gastric cancer (HDGC) syndrome. Methods Relevant literature dating from 1998 to 2021 was systematically searched for data on CDH1 gene. The Wilcoxon rank sum test and the Chi-square test were used to estimate if the difference observed between patients with gastric cancer (GC) and unaffected individuals was significant. Results We identified 80 families fulfilling the established clinical criteria for HDGC CDH1 genetic screening. There were more women than men with DGC and germline CDH1 variant (65.5%). Stratifying the age at diagnosis, we identified an association between DGC, positive CDH1 screening and young women (≤ 40 years) ( p = 0.015). The mean age at diagnosis was 39.6 ys for women and 42.5 ys for men. There was an association between CDH1 carrier status and DGC ( p = 0.021). Conclusions Young women carrying germline CDH1 variants with DGC are comparatively frequent in the HDGC syndrome, and potentially at higher risk to develop DGC particularly in low-incidence areas for GC.