Epidemiological studies of esophageal cancer in the era of genome-wide association studies

Table 1 Major risk factors for esophageal cancer

Risk factor	Ref.
Cigarette smoking (tobacco use)	Fan et al[12], Oze et al[7]
Alcohol drinking (alcohol consumption)1	Oze et al[13], Fan et al[12], Islami et al[5]
Drinking hot tea or soup at high temperature	Wu et al[14]
Food mutagens	Yokokawa et al[15], Zhang et al[16]
Family history	Turati et al[9], Gao et al[17]
Nutritional deficiency	Tran et al[18]
Poor oral hygiene/ESCC	Dar et al[8]
Coffee consumption2	Naganuma et al[11]
HPV infection	Li et al[19], Cui et al[20]
Obesity	Chen et al[21]

¹Alcohol consumption depends on the quantity of alcohol intake;

²Coffee consumption: reverse relation. ESCC: Esophageal squamous cell carcinoma.

Table 2 Genomic variants identified to be associated with esophageal squamous cell carcinoma

Loci associated with ESCC	Method/design	Case sample size	Control sample size	Ref.
PLCE1 (10q23 rs227422) and C20orf54 (20p13)	GWAS	1077	1733	Wang et al[22]
ALDH2 (4q21-23, rs671) and ADH1B (12q24, rs1229984)	GWAS	1070	2836	Cui et al[23]
PLCE1 (10q23 rs2274223)	GWAS	2115	3302	Abnet et al[24]
ALDH2 (4q23, rs671) and ADH1B (12q24.11–13, rs1229984)	GWAS	1071	2762	Tanaka et al[25]
5q11 (rs10052657) 21q22 (rs2014300), 6p21 (rs10484761), 10q23 (rs2274223), and 12q24 (rs2074356, rs11066280) CYP1A1 A2455G polymorphism(Ile/Val, rs1048943)	GWAS	2031 1881	2044 3786	Wu et al[26] Shen et al[27]
	Meta-analysis
	(13 case-control studies)
CYP1A1/CYP2E1 (MTHFR) C677T and A1298C polymorphisms with ESCC	Case-control study	565 /482 3213	468/466 4354	Wang et al[28] Fang et al[29]
	Meta-analysis
	(15 case-control studies)
rs1014867 polymorphisms in FAT4 gene	Case-control study	2139	2273	Du et al[30]
Interleukin 1B rs16944	Case-control study	380	380	Zheng et al[31]
CHRNA5-A3-B4 rs667282 TT/TG	Case-control study	866	952	Wang et al[32]
rs1494961, rs1229984 and rs1789924, and rs671	Case-control study	2139	2273	Gao et al[33]
Genetic variants in DNA repair pathway genes/(EGFR) signaling pathway	Case-control study	1942	2111	Li et al[34], Li et al[35]
Sex hormone metabolic genes	Case-control study	1026	1452	Hyland et al[36]
Chromosome 1 open reading frame 10 (C1orf10)	Case-control study	991	984	Zhang et al[37]

ESCC: Esophageal squamous cell carcinoma; GWAS: Genome wide association studies; PLCE1: Phospholipase C epsilon 1; C20orf54: Chromosome 20 open reading frame 54; ADH1B: Alcohol dehydrogenase; ALDH2: Acetaldehyde dehydrogenase.

Table 3 MicroRNA expression and their associations with esophageal squamous cell carcinoma[45]

MiRNA	Compared to normal esophageal tissue	Proved targets
miR-10a	Decreased	HOXA3, HOXB1, HOXB3
		HOXD4, HOXD10
miR-21	Increased	PCDCD4, NFIB, PTEN, TPM1
miR-93	Increased	FUSA, E2F1, TP53, INP1
miR-129	Increased	LATS2
miR-203	Increased/ decreased	ABL1, TP53INP1, SOCS3
miR-205	Decreased/increased	ZEB1, ZEB2, E2F5, HER3, ERBB3, PRKCE, LRP1
miR-375	Decreased	PDK1

Table 4 Common miRNA expression profiles in esophageal cancer[47]

ESCC		EAC
Up-regulated	Down-regulated	Up-regulated	Down-regulated
miR-21	Let-7c	miR-21	Let-7c
miR-155	miR-1	miR-28	miR-203
miR-93	MiR-99a	miR-3a-5p	miR-205
miR-129	miR-100	miR-143-145 cluster	miR-23a
	miR-133a	miR-192	miR-27a
	miR-143-145 cluster	miR-194	miR-27b
	miR-203	miR-215	miR-31
	miR-375		miR-99a
			miR-100

ESCC: Esophageal squamous cell carcinoma; EAC: Esophageal adenocarcinoma.