Discovering Rare Variants in Gastric Cancer Susceptibility in Gastric Cancer Family

Genome-wide association studies of gastric cancer (GC) cases have revealed common GC susceptibility loci with low effect size. We investigated rare variants with high effect size via whole-exome sequencing of subjects with familial clustering of GC.DNAs from the blood of 19 GC patients and 36 normal family members from 14 families with 2 or more GC patients were tested. Linkage analysis combined with association tests was performed to detect rare variants predisposing to GC. Based on the presence of germline variants, we conducted immunohistochemistry in both normal gastric mucosa and tumor tissues in order to characterize the underlying carcinogenic mechanism.