Dual primary gastric and colorectal cancer: The known hereditary causes and underlying mechanisms

Table 1 Inherited cancer predisposition syndromes related to dual primary gastric and colorectal cancer

Inherited syndrome/condition	Presentation	Clinical features	Inheritance type	Molecular/genetic defect/mutation	Ref.
Hereditary diffuse gastric cancer	Late presentation	GC and CRC	Autosomal dominant	Cadherin 1. Alpha-1 catenin. CTNNA1 gene	[8]
Familial adenomatous polyposis	Early (20s) asymptomatic, then diarrhoea, rectal bleeding, anaemia, CRC. GC (the proximal stomach)	Family history of colorectal polyps and CRC. Extraintestinal manifestations-osteoma, unruptured teeth. Extracolonic cancer (thyroid, duodenum, stomach, liver, bile ducts)	Autosomal dominant	APC gene. MUTYH mutation (MUTYH-associated polyposis)	[13,14]
Hereditary nonpolyposis colon cancer	Over the age of 50 yr	GC. CRC	Autosomal dominant	hMLH1 and hMSH2 genes. Instability of repeat nucleotide sequences or (microsatellites instability)	[15,17]
Lynch syndrome	Diagnosed at the age of 50-60 yr	GC. CRC. Others [endometrial cancer (54%)]. Ovarian cancer. Also, cancer of the pancreas, brain, kidney, and bile duct	Autosomal dominant	MMR genes (MLH1, MSH2, MSH6, and PMS2)	[18,19]
Peutz-Jeghers syndrome	At their 20s	CRC. Pancreatic, and gastric cancers. Others: Uterine, breast, ovarian, and lung	Autosomal dominant	STK11	[25,27]
Juvenile polyposis syndrome	In childhood but can occur at any age	Multiple hamartomas in the gastrointestinal tract. CRC. Duodenal, gastric, pancreatic cancers	Autosomal dominant in 75% and sporadic in 25%	SMAD4 gene (MADH4 gene) and the BMPR1A gene	[29-32]
PTEN hamartoma tumour syndrome and Cowden syndrome and others	Cancers are usually diagnosed at the age of 30-50 yr	Multiple hamartomas in the gastrointestinal tract. CRC. Breast, thyroid, kidney, endometrium, and gastric cancer (not common)	Autosomal dominant	PTEN germline mutations	[35]

GC: Gastric cancer; CRC: Colorectal cancer; STK11: Serine/threonine-protein kinase 11; APC: Adenomatous polyposis.