Relationship between genetic polymorphisms of ALDH2 and ADH1B and esophageal cancer risk: A meta-analysis

Table 1 Characteristics of studies of alcohol dehydrogenase-1B polymorphism and risk of esophageal cancer[15-27]

Study ID	Country, subjects	Cases	Controls	ADH1B
				Adjusted OR (95% CI)		Crude OR (95% CI)
				*1/*2 vs *2/*2	*1/*1 vs *2/*2	*1/*2 vs *2/*2	*1/*1 vs *2/*2
Yokoyama et al[15], 2006a	Japan, female	52	412	1.56 (0.56-4.35)	2.08 (0.76-5.56)	1.29 (0.7-2.4)	2.15 (0.81-5.7)
Boonyaphiphat et al[16], 2002a	Thailand	202	261	NAb	NA	1.15 (0.56-2.47)	2.01 (0.96-4.3)
Ding et al[17], 2009	China	221	191	1.21 (0.79-1.86)	2.78 (1.06-7.29)	1.30 (0.85-1.99)	2.42 (0.96-6.66)
Chao et al[18], 2000	China (Taiwan), alcoholics	88	327	NA	NA	1.61 (0.84-3.16)	4.85 (2.32-10.18)
Guo et al[19], 2008	China, male	80	480	2.89 (1.11-5.64)	NA	1.13 (0.66-1.93)	5.37 (2.45-11.46)
Li et al[20], 2008	Africa	220	241	-	-	-	-
Yang et al[21], 2005	Japan	165	494	1.57 (1.04-2.36)	0.62 (0.22-1.72)	2.08 (1.44-2.99)	1.12 (0.44-2.86)
Yang et al[22], 2007	China	191	198	1.89 (1.1-3.22)	1.91 (0.92-3.95)	1.35 (0.88-2.08)	1.92 (1.04-3.56)
Yokoyama et al[23], 2001a	Japan, alcoholic male	112	526	NA	NA	0.81 (0.46-1.43)	2.4 (1.48-3.88)
Yokoyama et al[24], 2002	Japan, male	234	634	NA	NA	1.16 (0.82-1.65)	5.73 (3.4-9.71)
Hori et al[25], 1997	Japan	94	130	1.7 (0.9-3.0)	6.2 (2.6-14.7)	1.33 (1.15-1.53)	6.2 (2.6-14.7)
Lee et al[26], 2008	China (Taiwan)	406	656	NA	NA	1.3 (0.97-1.73)	6.09 (4.07-9.23)
Hashibe et al[27], 2006	Europe	325	2550	NA	NA	0.64 (0.14-2.97)	0.85 (0.19-3.79)
Pooled results		2390	7100	1.60 (1.28-2.0)	2.17 (1.08-4.34)	1.32 (1.17-1.49)	2.91 (2.04-4.14)
P for heterogeneity				0.54	< 0.05	0.45	< 0.05

^aThe genotype frequencies among the controls differed significantly from the Hardy-Weinberg equilibrium (P < 0.05);

^bNA: Not available because not mentioned or calculated in the study. ADH1B: Alcohol dehydrogenase-1B; OR: Odds ratio; CI: Confidence interval.

Table 2 Characteristics of studies of aldehyde dehydrogenase-2 polymorphism and risk of esophageal cancer[15-26,28-33]

Study ID	Country, subjects	Cases	Controls	ALDH2
				Adjusted OR (95% CI)		Crude OR (95% CI)
				*1/*2 vs *1/*1	*2/*2 vs *1/*1	*1/*2 vs *1/*1	*2/*2 vs *1/*1
Yokoyama et al[15], 2006a	Japan, female	52	412	1.01 (0.54-1.87)	1.49 (0.47-4.78)	1.13 (0.62-2.06)	1.56 (0.5-4.88)
Boonyaphiphat et al[16], 2002a	Thailand	202	261	1.57 (0.89-2.76)	0.52 (0.05-5.33)	1.33 (0.82-2.17)	0.22 (0.03-1.87)
Ding et al[17], 2009	China, male	221	191	1.71 (1.1-2.66)	4.84 (2.25-10.61)	1.7 (1.08-2.68)	5.69 (2.51-12.18)
Chao et al[18], 2000	China (Taiwan), alcoholics	88	327	NAb	NA	3.54 (2.16-5.8)	1.33 (0.28-6.4)
Guo et al[19], 2008	China, male	80	480	NA	NA	1.5 (0.93-2.42)	0.1 (0.01-1.67)
Li et al[20], 2008a	Africa	237	268	NA	NA	1.24 (0.62-2.46)	2.73 (0.79-10.69)
Yang et al[21], 2005	Japan	165	494	6.43 (4.02-10.3)	1.92 (0.23-15.7)	2.08 (1.44-2.99)	1.12 (0.44-2.86)
Yang et al[22], 2007	China	191	198	1.67 (1.02-2.72)	0.26 (0.06-1.09)	1.35 (0.88-2.08)	1.92 (1.04-3.56)
Yokoyama et al[23], 2001	Japan, alcoholic male	112	526	13.50 (8.06-22.6)	-	11.8 (7.36-18.94)	Excludedc
Yokoyama et al[24], 2002	Japan, male	234	634	7.46 (4.71-11.81)	7.83 (1.33-46.08)	3.66 (2.62-5.1)	0.25 (0.06-1.07)
Hori et al[25], 1997	Japan	93	171	4.4 (2.5-7.7)	0.9 (0.2-3.6)	4.35 (2.42-7.83)	0.93 (0.24-3.55)
Lee et al[26], 2008	China (Taiwan)	406	656	NA	NA	2.88 (2.19-3.77)	0.91 (0.48-1.72)
Cai et al[28], 2006	China	205	394	0.76 (0.5-1.16)	1.72 (0.85-3.48)	0.69 (0.47-0.99)	2.25 (1.2-4.22)
Ding et al[29], 2002	China	98	235	NA	NA	0.91 (0.56-1.47)	0.24 (0.05-1.07)
Itoga et al[30], 2004	Japan, male	74	241	NA	NA	2.28 (2.19-3.77)	0.95 (0.2-4.57)
Matsuo et al[31], 2001	Japan	102	241	3.72 (1.88-7.36)	0.8 (0.09-6.88)	2.48 (1.52-4.03)	0.19 (0.025-3.52)
Yokoyama et al[32], 1996	Japan, male	29	28	NA	-	9.2 (4.22-20.07)	Excludedc
Yokoyama et al[33], 2006	Japan, alcoholic male	42	273	NA	NA	13.83 (6.16-31)	Excludedc
Pooled results		2631	6030	2.06 (1.09-3.89)	1.31 (0.52-3.34)	2.52 (1.76-3.61)	0.76 (0.42-1.40)
P for heterogeneity				< 0.001	< 0.001	< 0.001	< 0.001

^aThe genotype frequencies among the controls differed significantly from the Hardy-Weinberg equilibrium (P < 0.05);

^bNA: Not available;

^cNo studies were included because there were no cases and controls with ALDH2*2/*2. ALDH2: Aldehyde dehydrogenase-2; OR: Odds ratio; CI: Confidence interval.

Table 3 Risk of esophageal cancer associated with combinations of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 genotypes

Genotype	ALDH2 *1/*1 pooled OR (95% CI)	P for heterogeneity	ALDH2 *1/*2 pooled OR (95% CI)	P for heterogeneity
ADH1B *2/*2 or *1/*2
Never/rare drinkers[21,22]	1.00 (reference)	-	1.99 (0.53-7.5)	0.28
Moderate drinkers[21,22,26]	1.00 (reference)	-	5.64 (3.74-8.5)	0.68
Heavy drinkers[21-23,26]	1.00 (reference)	-	7.56 (3.4-16.78)	0.86
ADH1B *1/*1
Never/rare drinkers[21,22]	1.13 (0.22-5.7)	< 0.05	1.36 (0.41-4.51)	< 0.05
Moderate drinkers[21,22,26]	2.37 (1.13-4.97)	< 0.05	9.17 (0.6-140.38)	0.06
Heavy drinkers[21-23,26]	2.43 (1.48-3.99)	0.08	12.45 (2.9-53.46)	0.08

ALDH2: Aldehyde dehydrogenase-2; ADH1B: Alcohol dehydrogenase-1B; OR: Odds ratio; CI: Confidence interval.

Table 4 Risk of esophageal cancer associated with alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 polymorphisms according to ethnicity or sex

ADH1B	ADH1B*1/*1 vs *2/*2pooled OR (95% CI)	P for heterogeneity	ALDH2	ALDH2*1/*2 vs *1/*1 pooled OR (95% CI)	P for heterogeneity
Ethnicity
Chinese (Mainland)
Never/rare drinkers[17,22]	1.20 (0.54-2.66)	0.81	Never/rare drinkers[17,22]	1.75 (1.14-2.70)	0.06
Moderate drinkers[17,22]	1.86 (0.52-6.60)	0.22	Moderate drinkers[17,22]	1.98 (1.20-3.27)	0.34
Heavy drinkers[22]	3.55 (1.01-11.83)	-	Heavy drinkers[22]	1.31 (0.54-3.12)	-
Chinese (Taiwan)
Never/rare drinkers[18,26]	2.15 (0.99-4.69)	0.51	Never/rare drinkers[18,26]	1.14 (0.42-3.07)	-
Moderate drinkers[26]	3.93 (2.00-7.74)	-	Moderate drinkers[26]	6.21 (3.78-10.22)	0.67
Heavy drinkers[18,26]	3.36 (1.73-6.53)	0.3	Heavy drinkers[18,26]	9.21 (5.54-15.31)	0.76
Japanese
Never/rare drinkers[15,21,24]	2.41 (0.50-11.62)	0.31	Never/rare drinkers[15,21,24,30]	0.68 (0.33-1.42)	0.55
Moderate drinkers[15,21,24]	2.18 (0.38-12.23)	0.05	Moderate drinkers[15,21,24]	4.74 (3.29-6.83)	0.4
Heavy drinkers[15,21,23,24]	4.02 (1.83-8.80)	0.64	Heavy drinkers[15,21,23,24,32,33]	9.75 (7.34-12.97)	0.69
Sex
Male
Never/rare drinkers[17,21,22,24,26]	2.71 (1.13-6.51)	0.24	Never/rare drinkers[17,21,22,24,26]	1.92 (1.28-2.88)	0.55
Moderate drinkers[17,21,22,24,26]	3.93 (2.43-6.36)	0.39	Moderate drinkers[17,21,22,24,26]	3.53 (1.98-6.30)	< 0.05
Heavy drinkers[21-24,26]	3.22 (2.16-4.83)	0.39	Heavy drinkers[21-24,26,32,33]	7.04 (4.18-11.85)	< 0.05
Female
Never/rare drinkers[21,22,33]	1.48 (0.56-3.49)	0.17	Never/rare drinkers[21,22,33]	1.55 (0.50-14.78)	0.03
Moderate drinkers[21,22,33]	0.81 (0.21-3.15)	0.41	Moderate drinkers[21,22,33]	2.64 (1.24-5.68)	0.72
Heavy drinkers[22]	3.55 (1.06-11.84)	0.35	Heavy drinkers[21,33]	6.85 (1.04-44.95)	0.88

ALDH2: Aldehyde dehydrogenase-2; ADH1B: Alcohol dehydrogenase-1B; OR: Odds ratio; CI: Confidence interval.