Table 2.

Minimal and additional genes to include on multigene panel test for evaluation of colorectal cancer and/or polyposis

Genes	Cumulative CRC risk by age 70	Prevalence	Inheritance	Cancer/polyposis phenotype
Genes associated with Lynch syndrome
MLH1	4–79% [83–85]	1:1946 [16]	AD	CRC, EC, OV,GC, SBC, PC, HTC, UTC, PC, SC, BT
MSH2	35–77% [83–85]	1:2841 [16]
MSH6	12–50% [83–85]	1:758 [16]
PMS2a	10–19% [85, 86]	1:714 [16]
EPCAMb	75% [85]	Unknown
Genes associated with polyposis		syndromes
APC	69–100% [3]	2.29:100,000 to 3.2:100,000	AD	Adenomatous polyposis, CRC, SBC, GC, TC, HB, desmoids
BMPR1A	38%c [87, 88]	1:16,000 to 1:100,000	AD	Juvenile polyposis, CRC, GC, SBC
MUTYH	71.7–75.4% [33]	1:8073 [16] (biallelic)1:45 [16] (monoallelic)	AR	Adenomatous polyposis, CRC, SBC, TC
PTEN	9–16% [89, 90]	1:200,000 [91]	AD	Mixed polyposis (hamartomas, ganglioneuromas, serrated, adenomatous), BC, TC, EC, CRC, KC, melanoma
STK11	39% [23, 92]	1:25,000 to 1:280,000 [93]	AD	Peutz-Jeghers polyps, CRC, BC, PC, GC, SBC, OC, EC, SCT, LC
SMAD4	38%c [87, 88]	1:16,000 to 1:100,000	AD	Juvenile polyposis, CRC, GC, SBC

AD autosomal dominant, AR autosomal recessive, BC breast cancer, BT brain tumor, CRC colorectal cancer, EC endometrial cancer, GC gastric cancer, HB hepatoblastoma, HTC hepatobiliary tract cacner, KC kidney cancer, LC lung cancer, PC pancreatic cancer, SBC small bowel cancer, SC sebaceous carcinoma, SCT sex cord tumor, TC thyroid cancer, UTC urinary tract cancer

^aLaboratory analysis should be able to distinguish exons 12–15 in PMS2 from the transcribed pseudocopy of PMS2 (PMS2CL)

^bLarge rearrangement analysis only

^cEstimated cumulative lifetime colorectal cancer risk