Table 1.

Colorectal cancer-associated genes

Genes	Syndrome	Abbr.	Inheritance	Proportion of colorectal cancer	Tumour genetics	COSMIC mutational signatures v3a
MLH1 MSH2 MSH6 PMS2	Lynch syndrome (Constitutional mismatch repair-deficiency)	LS (CMMRD)	Dominant (Recessive)	~3% (Unknown)	MSI-H, hypermutated	SBS6, SBS15, SBS21, SBS26, SBS44, DBS7, DBS10, ID7, ID1c, ID2c
APC	(Attenuated) Familial adenomatous polyposis	AFAP/FAP	Dominant	~1%
MUTYH	MUTYH-associated polyposis	MAP	Recessive	<1%		SBS36
POLE POLD1	POLE/POLD1-associated tumour syndromeb	PPATS	Dominant	Unknown	Ultra- hypermutated	SBS10a, SBS10b, SBS14, SBS20, DBS3
NTHL1	NTHL1-associated tumour syndrome	NATS	Recessive	Unknown		SBS30
SMAD4 BMPR1A	Juvenile polyposis	JPS	Dominant	<1%
STK11	Peutz-Jeghers syndrome	PJS	Dominant	<1%
GREM1	Hereditary mixed polyposis syndrome	HMPS	Dominant	<1%
MSH3	MSH3-associated polyposis		Recessive	Unknown	EMAST
RNF43	Serrated polyposis syndrome	SPS	Dominant	Unknown	CIMP
PTEN	PTEN hamartoma tumour syndrome	PHTS	Dominant	<1%
TP53	Li-Fraumeni syndrome	LFS	Dominant	Unknown

^a https://cancer.sanger.ac.uk/cosmic/signatures/(8).

^bAlso known as polymerase proofreading-associated polyposis (PPAP).

^cMore than 10 000 mutations per tumour.

SBS, single base substitution signature; DBS, double base substitution signature; ID, insertion and deletion signature.