Genetic variations in colorectal cancer risk and clinical outcome

Table 1 Genome-wide association study-identified common genetic variants associated with colorectal cancer risk

SNP	Loci	Gene	Full name of gene	OR	P value	Pathway/function	Ref.	Method
Common biological pathway-related
rs12701937	7p14.1	GLI3 and INHBA	GLI family zinc finger 3 and inhibin, beta A	1.36	3.50E-05	MAPK signaling pathways	[11]	G
rs11014993	10p12.1	MYO3A	Myosin IIIA	1.22	2.00E-03	MAPK signaling pathways	[11]	G
rs59336	12q24.21	TBX3	T-box3	1.09	2.46E-06	Wnt pathway	[10]	G + M
rs4444235	14q22.2	BMP4	Bone morphogenetic protein 4	1.09	1.95E-11	BMP pathway	[21]	G
rs1957636	14q22.2	BMP4	Bone morphogenetic protein 4	1.08	1.36E-09	BMP pathway	[21]	G
rs16969681	15q13.3	GREM1	DAN family BMP antagonist	-	5.33E-08	BMP pathway	[21]	G
rs4779584	15q13.3	GREM1	DAN family BMP antagonist	-	5.27E-03	BMP pathway	[21]	G
rs11632715	15q13.3	GREM1	DAN family BMP antagonist	-	2.30E-10	BMP pathway	[21]	G
rs4939827	18q21	SMAD7	SMAD family member 7	1.2	7.80E-28	TGF-β1 pathway, cell arrest, cell proliferation	[5,6,19]	G
rs12953717	18q21	SMAD7	SMAD family member 7	1.17	9.10E-12	TGF-β and Wnt signaling	[5]	G
rs4464148	18q21	SMAD7	SMAD family member 7	1.15	6.66E-08	TGF-β and Wnt signaling	[5]	G
rs961235	20p12.3	BMP2	Bone morphogenetic protein 2	1.12	4.45E-16	BMP pathway	[21]	G
rs4813802	20p12.3	BMP2	Bone morphogenetic protein 2	1.09	7.52E-11	BMP pathway	[21]	G
rs6038071	20p13	CSNK2A1	Casein kinase 2, alpha 1 polypeptide	2.64	3.00E-04	MAPK signaling pathways	[11]	G
Genome instability-related
rs11903757	2q32.3	NABP1	Nucleic acid binding protein 1	1.16	9.50E-08	DNA repair, genomic stability	[10]	G + M
rs647161	5q31.1	PITX1	Paired-like homeodomain transcription factor 1	1.11	1.22E-10	RAS pathway; activate TP53; telomerase activity	[29]	G + M
rs1321311	6p21	CDKN1A	Cyclin-dependent kinase inhibitor 1A	1.1	1.14E-10	Microsatellite instability, DNA repair, genomic instability	[26]	G + M
rs3824999	11q13.4	POLD3	Polymerase DNA- directed δ3	1.08	3.65E-10	DNA mismatch and base-excision repair	[26]	G + M
rs78378222	17p13	TP53	Promotor region of TP53 gene	1.39	1.60E-04	TP53	[63]	G
Cell cycle control-related
rs10911251	1q25.3	LAMC1	Laminin gamma 1	1.09	5.90E-08	Gene transcription	[10]	G + M
rs6691170	1q41	DUSP10	Dual-specificity phosphatase	1.06	9.55E-10	Inactivates p38 and SAPK	[9]	M
rs6687758	1q41	DUSP10	Dual-specificity phosphatase	1.09	2.27E-09	Inactivates p38 and SAPK	[9]	M
rs886774	7q31	LAMB1	Laminin β1	1.17	3.00E-08	Anchoring the single-layered epithelium, ulcerative colitis	[33]	G
rs3802842	11q23	POU2AF1	POU class 2 associating factor 1	1.1	5.80E-10	Growth of multiple myeloma cells	[6]	G
rs10774214	12p13.32	CCND2	Cyclin D2	1.09	3.06E-08	Cell-cycle transition	[29]	G + M
rs3217810	12p13.32	CCND2	Cyclin D2	1.2	3.70E-07	Cell-cycle transition	[10]	G + M
rs3217901	12p13.32	CCND2	Cyclin D2	1.1	< 5.0E-7	Cell-cycle transition	[10]	G + M
rs11169552	12q13.13	DIP2	Disco-interacting protein 2B	1.09	1.89E-10	Cell morphogenesis	[9]	M
rs1728785	16q22	CDH1	E-cadherin,	1.17	2.80E-08	Epithelial restitution, repair following mucosal damage, active colitis	[33]	G
rs10411210	19q13.33	RHPN2	Rho GTPase binding protein 2	1.15	5.00E-09	Actin cytoskeleton	[20]	G + M
rs4925386	20q13.33	LAMA5	Large laminin A5	1.08	1.89E-10	BMP pathway	[9]	M
rs5934683	Xp22.2	SHR00M2	Shroom family member 2	1.07	7.30E-10	Cell morphogenesis	[26]	G + M
Gene expression and regulation-related
rs16892766	8q23.3	EIF3H	Eukaryotic translation initiation factor 3, subunit H	1.25	3.30E-18	Translation initiation	[8]	G
rs7014348	8q24	POU5FIP1	POU class 5 homeobox 1B	1.19	8.60E-26	Weak transcriptional activator	[6]	G
rs7136702	12q13.13	ATF1	Activating transcription factor 1	1.06	4.02E-08	Transcription	[9]	M
rs6017342	20q13.12	HNF4A	Transcription factor hepatocyte nuclear factor 4α	1.11	3.20E-17	Transcription	[33]	G
Gene desert and others
rs7524102	1p36.12	-	-	1.1	3.10E-07	-	[33]	G
rs16823149	1q31	Clorf21	-	-	5.50E-08	-	[11]	G
rs4574118	2q12	PLGLA	Plasminogen-like A, non-coding RNA	-	1.80E-07	-	[11]	G
rs10936599	3q26.2	MYNN	Myoneurn gene	1.08	3.39E-08	Unknown	[9]	M
rs4140904	4p15.3	NCAPC	Non-SMC condensing I complex, subunit G	-	1.40E-07	-	[11]	G
rs7758229	6q26-27	SLC22A3	organic cation transporter	1.28	7.92E-09	Transport of cationic drugs, toxins, and endogenous metabolism	[19]	G
rs6983267	8q24	-	-	1.18	1.51E-08	-	[19]	G
rs7837328	8q24	-	-	1.17	7.44E-08	-	[19]	G
rs2209907	9q21.3	TLE4	Transducin-like enhancer of spit 4	-	3.40E-08	-	[11]	G
rs10795668	10p14	-	-	1.12	2.50E-13	-	[8]	G
rs9548988	13q13.3	-	-	1.1	2.70E-07	-	[33]	G
rs2423279	20p12.3	PLCB1	Phospholipase C-beta 1	1.1	6.64E-09	Unknown	[29]	G + M

SNP: Single nucleotide polymorphisms; G: Genome-wide association study; M: Meta-analysis; G + M: Combination of GWAS and meta-analysis; BMP: Bone morphogenetic protein; MAPK: Mitogen-activated protein kinase; TGF-β: Transforming growth factor; GWAS: Genome-wide association study.