Polymorphisms in mucin genes in the development of gastric cancer

Table 1 List of association studies between polymorphisms in mucin genes and development of gastric cancer

Gene	Ref.	Population	Disease	Study design	Sample (case/control)	Polymorphism	Association
MUC1	Vinall et al[28]	European	H. pylori related gastritis	Case–control study	57 gastritis patients	VNTR	Yes
	Carvalho et al[34]	Portuguese	GC	Case–control study	159/324	VNTR	Yes
	Silva et al[35]	Portuguese	CAG, IM	Case–control study	174 patients	VNTR	Yes
	Abnet et al[37]	Chinese	GC	GWAS	1625/2100	rs4072037	Yes
					Replication: 615/1202		No
					Combined: 2240/3302		No
	Saeki et al[39]	Japanese	DGC	Case–control study	606/1264/	rs4072037, rs2070803	Yes
		Japanese			304/1465	rs4072037, rs2070803	Yes
		South Korean			452/372	rs4072037, rs2070803	Yes
	Xu et al[40]	Chinese	GC	Case–control study	138/241	rs4072037	Yes
	Jia et al[43]	Polish	GC	Case–control study (tag SNP approach)	273/377	rs6427184	Yes
						rs4971052	Yes
						rs4276913	Yes
						rs4971088	Yes
						rs4971092	Yes
						rs4072037	Yes
	Jia et al[43]	Polish	H. pylori infection	Case–control study (tag SNP approach)	320/57	rs6427184	No
						rs4971052	No
						rs4276913	No
						rs4971088	No
						rs4971092	No
						rs4072037	No
	Zhang et al[44]	Chinese	GC	Case–control study	1681/1858	rs4072037	Yes
	Palmer et al[45]	Caucasian	GC	Case–control study	596/587	rs4072037	Yes
	Li et al[46]	Chinese	GC	Case–control study	300/300	rs2070803	Yes
	Zhang et al[47]	Chinese	Non-cardia GC	Case–control study	288/281	rs4072037	No
				(tag SNP approach)		rs2990245	No
						rs9628662	No
						rs9426886	No
	Zhang et al[47]	Chinese	H. pylori infection	Case–control study	122/159	rs4072037	No
				(tag SNP approach)		rs2990245	No
						rs9628662	No
						rs9426886	No
	Frank et al[48]	German	CAG	Case–control study	533/1054	rs4072037	No
	Marín et al[49]	Spanish	GCPLs	Case–control study	387 patients	rs3814316	No
				(tag SNP approach)		rs9426886	No
						rs1045253	No
	Sun et al[50]	Hispanic American	GC	Case–control study	132/125	rs4072037	No
	Duan et al[51]	-	GC	Meta-analysis	4220/6384	rs4072037	Yes
	Zheng et al[52]	-	GC	Meta-analysis	6580/10324	rs4072037	Yes
	Mocellin et al[42]	Asian	DGC	Meta-analysis	7279 subjects	rs2070803	Yes
MUC5AC	Jia et al[43]	Polish	GC	Case–control study (tag SNP approach)	273/377	rs1541314	No
						rs2014486	Yes
						rs2075859	No
						rs2672785	No
						rs2735733	Yes
						rs7118568	No
						rs868903	Yes
						rs4963049	No
	Jia et al[43]	Polish	H. pylori infection	Case–control study (tag SNP approach)	320/57	rs1541314	No
						rs2014486	No
						rs2075859	No
						rs2672785	No
						rs2735733	No
						rs7118568	No
						rs868903	No
						rs4963049	No
	Zhou et al[61]	Chinese	Non-cardia GC	Case–control study (tag SNP approach)	288/281	rs3793966	No
						rs7118568	No
						rs868903	No
						rs3793964	Yes
						rs3750919	No
						rs5743942	No
						rs4963062	No
						rs885454	Yes
						rs6578810	No
						rs11040869	Yes
						rs7118481	No
						rs7105198	No
	Zhou et al[62]	Chinese	H. pylori infection	Case–control study	122/159	rs3793966	No
				(tag SNP approach)		rs7118568	No
						rs868903	No
						rs3793964	No
						rs3750919	No
						rs5743942	No
						rs4963062	No
						rs885454	No
						rs6578810	No
						rs11040869	No
						rs7118481	No
						rs7105198	No
	Wang et al[63]	Chinese	GC	Case–control study	230/328	VNTR	Yes
MUC6	Nguyen et al[68]	-	H. pylori infection	Case–control study	92/68	VNTR	Yes
	Garcia et al[69]	Portuguese	GC	Case–control study	157/376	VNTR	Yes
	Kwon et al[70]	South Korean	GC	Case–control study	470/1103	VNTR	Yes
	Jia et al[43]	Polish	GC	Case–control study (tag SNP approach)	273/377	rs1128413	No
						rs4077293	No
						rs7483870	No
						rs7943115	No
						rs11602663	No
						rs11605303	No
						rs10902076	No
						rs2071174	No
						rs11245936	No
						rs10794359	No
						rs7112267	No
						rs12574439	No
						rs7119740	No
						rs11601642	No
	Jia et al[43]	Polish	H. pylori infection	Case–control study (tag SNP approach)	320/57	rs1128413	No
						rs4077293	No
						rs7483870	No
						rs7943115	No
						rs11602663	No
						rs11605303	No
						rs10902076	No
						rs2071174	No
						rs11245936	No
						rs10794359	No
						rs7112267	No
						rs12574439	No
						rs7119740	No
						rs11601642	No
	Marín et al[49]	Spanish	GCPLs	Case–control study	387 patients	rs4076950	No
				(tag SNP approach)		rs7481521	No
						rs11246384	No
						rs6597947	No
						rs9794921	No
	Frank et al[48]	German	CAG	Case–control study	533/1054	rs7481521	No
MUC2	Jeong et al[72]	South Korean	GC	Case–control study	455/457	VNTR	Yes
	Marín et al[49]	Spanish	GCPLs	Case–control study	387 patients	rs10902073	Yes
				(tag SNP approach)		rs10794281	Yes
						rs2856082	No
						rs2071174	Yes
						rs7396030	No
						rs11245936	No
						rs7944723	Yes
						rs6421972	No
						rs10794293	Yes
						rs11245954	No
						rs7480563	No
						rs7126405	No
						rs3924453	Yes
						rs4077759	Yes
	Frank et al[48]	German	CAG	Case–control study	533/1054	rs2856111	No
						rs11825977	No

CAG: Chronic atrophic gastritis; DGC: Diffuse gastric cancer; GCPLs: Gastric cancer precursor lesions; H. pylori: Helicobacter pylori; IM: Intestinal metaplasia; SNP: Single nucleotide polymorphism; GC: Gastric cancer.

Table 2 Description of the studied single nucleotide polymorphisms in mucin genes

Gene	Chromosome	SNPs	Wild alleles	Mutated alleles	Contig position1	Location2
MUC1	1q21	rs4072037	A	G	12007689	T22T
		rs2070803	C	T	12000652	3’ flanking region
		rs6427184	A	G	11965720	3’ flanking region
		rs4971052	C	T	11968955	3’ flanking region
		rs4276913	A	G	11974610	3’ flanking region
		rs4971088	T	A	11985820	3’ flanking region
		rs4971092	T	C	11986883	3’ flanking region
		rs2990245	T	C	12043084	5’ flanking region
		rs9628662	T	G	12051963	5’ flanking region
		rs9426886	T	A	11994691	3’ flanking region
		rs3814316	C	T	11992655	3’ flanking region
		rs1045253	T	C	12046857	5’ flanking region
MUC5AC	11p15.5	rs1541314	G	A	1182293	3’ flanking region
		rs2014486	A	G	1177573	3’ flanking region
		rs2075859	C	T	1169258	3’ flanking region
		rs2672785	C	T	1165711	3’ flanking region
		rs2735733	C	T	1180410	3’ flanking region
		rs7118568	C	G	1162850	3’ flanking region
		rs868903	T	C	1161460	3’ flanking region
		rs4963049	A	G	1155197	3’ flanking region
		rs3793966	C	T	1221718	3’ flanking region
		rs3793964	C	T	1220752	3’ flanking region
		rs3750919	G	A	1211601	3’ flanking region
		rs5743942	C	T	1232798	3’ flanking region
		rs4963062	G	A	1245411	3’ flanking region
		rs885454	C	T	1162161	3’ flanking region
		rs6578810	T	G	1209349	3’ flanking region
		rs11040869	G	A	1203382	3’ flanking region
		rs7118481	G	C	1267108	3’ flanking region
		rs7105198	G	C	1086133	5’ flanking region
MUC6	11p15.5	rs1128413	C	T	950694	3’ flanking region
		rs4077293	C	T	936522	3’ flanking region
		rs7483870	C	T	916019	3’ flanking region
		rs7943115	G	A	913885	3’ flanking region
		rs11602663	C	T	960778	Intronic
		rs11605303	G	A	978110	5’ flanking region
		rs10902076	G	C	1006044	5’ flanking region
		rs2071174	C	T	1013712	5’ flanking region
		rs11245936	G	A	1026266	5’ flanking region
		rs10794359	C	T	991715	5’ flanking region
		rs7112267	C	T	996981	5’ flanking region
		rs12574439	G	C	997948	5’ flanking region
		rs7119740	C	G	1000419	5’ flanking region
		rs11601642	C	A	1002509	5’ flanking region
		rs4076950	C	T	955021	Intronic
		rs7481521	G	A	967811	V619M
		rs11246384	C	T	970448	Intronic
		rs6597947	G	T	977029	5’ flanking region
		rs9794921	G	T	979867	5’ flanking region
MUC2	11p15.5	rs10902073	C	A	1000934	5’ flanking region
		rs10794281	C	T	1003149	5’ flanking region
		rs2856082	C	G	1011562	5’ flanking region
		rs2071174	C	T	1013712	5’ flanking region
		rs7396030	C	T	1025368	Intronic
		rs11245936	G	A	1026366	G832S
		rs7944723	C	G	1039802	P1832P
		rs6421972	G	A	1042586	I2154T
		rs10794293	C	T	1045031	Intron
		rs11245954	A	G	1047170	V2459V
		rs7480563	G	A	1047741	T2524P
		rs7126405	G	A	1049388	Q2653P
		rs3924453	G	A	1051898	3’ flanking region
		rs4077759	C	T	1052068	3’ flanking region
		rs2856111	T	C	1015747	L58P
		rs11825977	A	G	1015920	V116M

¹Based on contig NT_004487.20 for MUC1 gene, and contig NT_009237.19 for MUC5AC, MUC6 and MUC2 genes;

²SNP location relative to each gene in the region. SNPs: Single nucleotide polymorphisms.