The findings of this prospective study indicate that one in every four GC patients with hereditary high risk factors may carry pathogenic/likely pathogenic cancer-susceptibility gene variants, which were identified in nine genes: MLH1 (n = 1), MSH2 (n = 1), CDH1 (n = 1), BLM (n = 1), PALB2 (n = 1), EXT2 (n = 1), CHEK2 (n = 1), ERCC2 (n = 1), and SPINK1 (n = 2). This evidence concerns the gene MSH2 and cancer.