Table 2. Clinical syndromes and genes associated with hereditary gastric cancer.

Syndrome	Gene (s)	Clinical criteria suggesting this diagnosis	Gastric cancer risk	Risks for other cancers
Hereditary diffuse gastric cancer (HDGC)	CDH1	Diffuse gastric cancer (DGC) and an FH of one or more first- or second-degree relatives with GC; or personal and/or FH of DGC diagnosed before the age of 40; or personal and/or FH of DGC and LBC, one diagnosed before the age of 50. Obs.: the majority of gastric cancers are of the diffuse type.	70%–80%	Breast (lobular)
Juvenile polyposis (JPS)	SMAD4 BMPR1A	Presence of five or more juvenile polyps in the colorectum or any juvenile polyps in other parts of the GI tract.	20%–30%	Duodenal, colorectal
Peutz-Jeghers (PJS)	STK11	Presence of perioral or buccal hyperpigmented spots and/or two or more histologically characteristic GI hamartomatous polyp(s) or a solid tumour typical of PJS or a family history of the syndrome.	29%	Breast (any), ovary, colorectal, pancreatic.
Lynch (LS)	MLH1 MSH2 MSH6 PMS2 EPCAM	GC with personal or FH consistent with LS (Amsterdam or Bethesda criteria [20]; Tumour with mismatch repair deficiency detected by IHC or MSI testing; Known family pathogenic variant in a LS gene;Risk of ≥5% chance of LS based on risk prediction models; Obs.: the majority of GC in LS are of the intestinal type.	5%–13%	Duodenal, colorectal, ovarian, endometrial, urinary tract, pancreatic
Li-Fraumeni (LFS)	TP53	Personal or FH consistent with the Chompret criteria for LFS [104].	1%–4%	Breast (any), CNS, sarcomas, lung, adrenal cortical and other.
Familial adenomatous polyposis (FAP)	APC	Presence of ≥100 synchronous colorectal adenomas (“classic” FAP) or 10–99 synchronous adenomas (attenuated FAP).	0.6%	Duodenal, colorectal, thyroid
Cowden (CS)	PTEN	Presence of multiple GI hamartomas or ganglioneuromas and a group of major and minor criteria including other solid tumours and non-tumoural findings [39]	Increased, but exact % not determined	Breast (any), endometrial, thyroid.