Clinical and molecular features of young-onset colorectal cancer

Table 1 Clinicopathologic and molecular differences between young-onset and late-onset colorectal cancer

Clinical and molecular characteristics	Young-onset CRC( ≤50 yr)	Late-onset CRC(> 50 yr)
Proximal colon		X
Distal colon and rectum	X
Synchronous and metachronous CRC	X
Later stage at diagnosis (stage III/IV)	X
Mucinous/signet ring and poorly differentiated features	X
Typically MSS	X
MSI due to MLH1 gene promoter methylation		X
CIN		X
CIMP-low	X
CIMP-high		X
Microsatellite and chromosome stable CRC	X
Hypomethylation of LINE 1	X

CRC: Colorectal cancer; MSS: Microsatellite stable; MSI: Microsatellite instability; CIN: Chromosomal instability; CIMP: CpG island methylator phenotype; MACS: Microsatellite and chromosome stable CRC.

Table 2 Clinical and molecular features associated with hereditary colorectal cancer syndromes

Hereditary CRC syndrome	Age of presentation	Gene(s)	Clinical features
Lynch syndrome	Average age of diagnosis of CRC is 42-45 yr	MLH1, MSH2	Lifetime risk of CRC 70%
		MSH6,PMS2,EPCAM	Risk of extracolonic cancers
Classic FAP	Average age of diagnosis of CRC is 39 yr	APC	100-1000 adenomas
		MUTYH (biallelic)	CRC risk 90% without colectomy
			Risk of extracolonic cancers
Attenuated FAP	Average age of diagnosis of CRC is 51 yr	APC, MUTYH mutations detected in approximately 10%	10-99 adenomas
PJS	Polyps occur during childhood and early adulthood	STK11	Mucocutaneous pigmentation
			≥ 2 hamartomatous polyps in small bowel
			Lifetime cancer risks 80%-90%
JPS	Late childhood or early adolescence	SMAD4, BMPR1A, ENG	> 3-5 juvenile polyps in the gastrointestinal tract
			Congenital cardiac valvular disease and/or atrial and ventricular septal defects
PPAP	Second through fourth decades of life	POLE	Oligo adenomatous polyposis
		POLD1	Young-onset CRC
			Endometrial cancer
Cowden disease	Second and third decades of life	PTEN	Variable CRC risk
			Macrocephaly
			Increased risk of thyroid, breast, and endometrial cancer

CRC: Colorectal cancer; FAP: Familial adenomatous polyposis; PJS: Peutz-Jeghers syndrome; JPS: Juvenile polyposis syndrome; PPAP: Polymerase Proofreading-Associated Polyposis.