Table 3.

Additional genes with (a) low to moderately increased risk of colorectal cancer (CRC), (b) preliminary but limited data on CRC risk, and (c) genes with pathogenic variants found in CRC patients that are actionable in regard to other cancers but CRC causation not proven. Testing for these genes can be considered in specific circumstances

Genes	Odds ratio	Prevalence	Inheritance	Cancer/polyposis phenotype
(a) Genes associated with low to moderately increased risk of CRC
ATM	2.81–2.97 [27]	1:100 [94]	AD	BC, PC
CHEK2	1.56–1.88a [95]	1:100 to 1:200 [28]	AD	BC, CRC
TP53	Not defined, but skewed towards younger age at diagnosis [96, 97]	1:5000 to 1:20,000	AD	ACC, BC, BT, CRC, LC, leukemia, sarcoma
(b) Genes with preliminary but limited data
SCG5/GREM1b	Not defined, presumed to be high	Unknown	AD	Mixed (serrated, juvenile, adenomatous) polyposis, CRC
POLD1	Not defined	Unknown	AD	Adenomatous polyposis, BT, CRC, EC
POLE	Not defined	Unknown	AD	Adenomatous polyposis, CRC
AXIN2	Not defined	Unknown	AD	Adenomatous polyposis, CRC
NTHL1	Not defined	Unknown	AR	Adenomatous polyposis, CRC
MSH3	Not defined	Unknown	AR	Adenomatous polyposis, CRC
GALNT12	Not defined	Unknown	AD	CRC
RPS20	Not defined	Unknown	AD	CRC
(c) Genes with PV found in CRC patients that are actionable but CRC causation not proven
BRCA1	Not defined	1:400 to 1:500 [98] 1:40 (Ashkenazi Jewish) [99]	AD	BC, OC, PrC, melanoma
BRCA2	Not defined	1:400 to 1:500 [98] 1:40 (Ashkenazi Jewish) [99]	AD	BC, OC, PrC, melanoma
CDKN2A	Not defined	Unknown	AD	PC, melanoma
PALB2	3.42–4.91 [27]	Unknown	AD	BC, PC

ACC adrenal cortical carcinoma, AD autosomal dominant, AR autosomal recessive, BC breast cancer, BT brain tumor, CRC colorectal cancer, GC gastric cancer, LC lung cancer, PC pancreatic cancer, PrC prostate cancer, PV pathogenic variant

^aData limited to CHEK2 c.1100delC and p.I157T

^bLarge rearrangement analysis only