Gene, genetics and genetic medicines in gastroenterology: Current status and its future

Table 6 Germline testing available for screening

No.	GI disorder/syndrome	Guideline source	Genes recommended for testing	Testing criteria
1	Lynch syndrome (hereditary nonpolyposis colorectal cancer)	ACG, NCCN, ESMO	MLH1, MSH2, MSH6, PMS2, EPCAM	Personal/family history of colorectal, endometrial, or other LS-associated cancers; tumor MSI or IHC abnormality
2	Familial adenomatous polyposis (FAP)	ACG, NCCN	APC	> 100 colorectal adenomas or family history of FAP
3	Attenuated FAP	ACG	APC	Patients with 10-99 adenomas
4	MUTYH-associated polyposis	ACG	MUTYH (biallelic)	Multiple adenomas and autosomal recessive inheritance
5	Peutz-Jeghers syndrome	NCCN, ESMO	STK11	Mucocutaneous pigmentation and hamartomatous polyps; family history
6	Juvenile polyposis syndrome	ACG, NCCN	SMAD4, BMPR1A	≥ 5 juvenile polyps or family history
7	Cowden syndrome/PTEN hamartoma tumor syndrome	NCCN	PTEN	GI polyps with mucocutaneous lesions or macrocephaly
8	Hereditary pancreatic cancer	NCCN	BRCA1/BRCA2, PALB2, ATM, CDKN2A, STK11	Family history of pancreatic cancer or known mutation
9	Hereditary diffuse gastric cancer	NCCN	CDH1	Family history of diffuse gastric cancer or lobular breast cancer
10	Serrated polyposis syndrome	WHO, ACG	No known high-penetrance genes; RNF43 under investigation	Multiple serrated polyps meeting WHO criteria

FAP: Familial adenomatous polyposis; ACG: American College of Gastroenterology; NCCN: National Comprehensive Cancer Network; ESMO: European Society for Medical Oncology; WHO: World Health Organization; LS: Lynch syndrome; MSI: Microsatellite instability; GI: Gastrointestinal; IHC: Immunohistochemistry.