New genes emerging for colorectal cancer predisposition

Table 1 Hereditary colorectal cancer genes

	Gene	Chromosome	Mendelian pattern	Function
Familial adenomatous polyposis	APC	5q	AD	Regulation of canonical Wnt signaling pathway
	MUTYH	1p	AR	Base-excision repair
Hereditary non-polyposis CRC (Lynch syndrome)	MLH1	3p	AD	Mismatch repair
	MSH2	2p	AD	Mismatch repair
	MSH6	2p	AD	Mismatch repair
	PMS2	7p	AD	Mismatch repair
Peutz-Jeghers	LKB1	19p	AD	Regulation of Wnt signaling pathway
Juvenile polyposis	SMAD4	18q	AD	TGFBR signaling pathway
	BMPR1A	10q	AD	TGFBR signaling pathway
Cowden’s disease	PTEN	10q	AD	Negative regulation of PI3K signaling
	KLLN	10q	AD	Apoptotic process

CRC: Colorectal cancer; AD: Autosomal dominant; AR: Autosomal recessive; TGFBR: Transforming growth factor beta receptor; PI3K: Phosphatidylinositol 3-kinase.

Table 2 Amsterdam criteria in Lynch syndrome

Amsterdam criteria I	Amsterdam criteria II
At least three relatives with CRC; all of the following must be met:	At least three relatives with colorectal, endometrial, small bowel, ureter, or renal pelvis cancer; all of the following must be met:
One affected individual is a first degree relative of the other two	One affected individual is a first degree relative of the other two
At least two successive generations affected	At least two successive generations affected
At least one CRC diagnosed before the age of 50 years	At least one tumor diagnosed before the age of 50 years
Familial adenomatous polyposis has been excluded	Familial adenomatous polyposis has been excluded

CRC: Colorectal cancer.

Table 3 Genetic variants associated with colorectal cancer susceptibility identified by genome-wide association studies (as for September 2013)

SNP	Region	Gene	Sample size (cases/controls)	Effect size OR (95%CI)
rs693267	8q24.21	MYC	8264/6206	1.21 (1.15-1.27)
rs4939827	18q21.1	SMAD7	8413/6949	1.18 (1.12-1.23)
rs16892766	8q23.3	EIF3H	18831/18540	1.25 (1.19-1.32)
rs3802842	11q23.1	?	14500/13294	1.12 (1.07-1.17)
rs4779584	15q13.3	GREM1	7922/6741	1.26 (1.19-1.34)
rs10795668	10p14	?	18831/18540	1.12 (1.10-1.16)
rs4444235	14q22.2	BMP4	20288/20971	1.11 (1.08-1.15)
rs9929218	16q22.1	CDH1	20288/20971	1.10 (1.06-1.12)
rs10411210	19q13	RHNP2	20288/20971	1.15 (1.10-1.20)
rs961253	20p12.3	BMP2	20288/20971	1.12 (1.08-1.16)
rs6691170	1q41	DUSP10	18185/20197	1.06 (1.03-1.09)
rs10936599	3q26.2	TERC	18185/20197	0.93 (0.91-0.96)
rs11169552	12q13.3	?	18185/20197	0.92 (0.90-0.95)
rs4925386	20q13.33	LAMA5	18,185/20,197	0.93 (0.91-0.95)
rs1957636	14q22.2	BMP4	24910/26275	1.08 (1.05-1.11)
rs4813802	20p12.3	BMP2	24910/26275	1.09 (1.06-1.12)
rs2736100	5p15.33	TERT	16039/16430	1.07 (1.04-1.10)
rs1321311	6p21	CDKN1A	21096/19555	1.10 (1.07-1.13)
rs3824999	11q13.4	POLD3	21096/19555	1.10 (1.07-1.13)
rs5934683	Xp22.2	SHROOM2	21096/19555	1.07 (1.04-1.10)
rs12080929	1p33	SLC5A9	2317/2447	0.86 (0.78-0.95)
rs11987193	8p12	DUSP4	2317/2447	0.78 (0.70-0.87)
rs10774214	12p13.32	CCND2	11870/14190	1.04 (1.00-1.09)
rs647161	5q31.1	PITX1	11870/14190	1.07 (1.02-1.11)
rs2423279	20p12.3	HAQ1	11870/14190	1.07 (1.03-1.12)
rs11903757	2q32.3	NABP1	15752/21771	1.16 (1.10-1.22)
rs10911251	1q25.3	LAMC1	15752/21771	1.09 (1.06-1.13)
rs3217810	12p13.32	CCND2	13654/16022	1.20 (1.12-1.28)
rs3217901	12p13.32	CCND2	15752/21771	1.10 (1.06-1.14)
rs59336	12q24.21	TBX3	15752/21771	1.09 (1.06-1.13)